Ann Thorac Cardiovasc Surg. 2014;20(3):202-6.

Clinical-pathological findings of catamenial pneumothorax: comparison between recurrent cases and non-recurrent cases.

Haga T1Kurihara MKataoka HEbana H.

 

Abstract

PURPOSE:

Catamenial pneumothorax (CP) is classified as thoracic endometriosis syndrome. There are few reports of CP, and the clinical manifestations of this disease are unclear. The aim of the present study is to clarify the features of CP.

METHODS:

The clinical and pathological files of the 92 female patients pathologically diagnosed with thoracic endometriosis are included in this study. The clinical data and pathological findings of the recurrent and non-recurrent groups are compared.

RESULTS:

Thirty-six patients (39.1%) experienced recurrence, 37 (40.2%) patients did not, and 19 (20.4) patients could not be evaluated. The ratio of the endometrial gland in the diaphragm is significantly higher in the recurrent cases in comparison to non-recurrent cases (66.7% vs. 37.8%, P = 0.01).

CONCLUSIONS:

The recurrence rate of CP is high. Further study of the optimal management strategies is needed, especially for CP cases with the endometrial gland in the diaphragm.

 

 

Arch Gynecol Obstet. 2013 Dec;288(6):1295-300.

Immunohistochemical alterations of cajal-like type of tubal interstitial cells in women with endometriosis and tubal ectopic pregnancy.

Yang XJ1Xu JYShen ZJZhao J.

 

Abstract

PURPOSE:

The aim of the study was to observe alterations of pacemaker cells termed cajal-like type of tubal interstitial cells (t-ICC) in oviduct from early-stage EMs and tEP, discuss underlying mechanisms and potential role in tubal factor infertility (TFI).

METHODS:

Ten patients with early-stage EMs, 10 with unruptured tEP and 10 control subjects were included in this retrospective comparative study, received adnexectomy (salpingectomy) and/or hysterectomy. Paraffin-embedded full-thickness isthmic segment of oviduct specimens received immunohistochemistry with c-kit/CD117 antibody. Network distribution and area density of cells with features of t-ICC were analyzed.

RESULTS:

t-ICC was detected mainly in lamina propria and smooth muscle layers. t-ICC lost its network integrity, became less densely stained, sparse and almost invisible with relatively very rare connections in EMs and tEP, apparently differing in morphology of t-ICC from control, which demonstrated rich t-ICC immunostaining and intact network. Further quantitative analysis showed the area density of t-ICC decreased significantly in early-stage EMs and tEP compared with the control (73.9 ± 8.8 vs. 156 ± 18.3 mm(2); and 76 ± 7.4 vs. 156 ± 18.3 mm(2); both P < 0.001).

CONCLUSIONS:

We revealed that t-ICC underwent certain degree of cell damage, suggested that decreased expression of t-ICC network may be involved in early development of EMs and tEP, and might serve as an explanation for TFI in these patients.

 

 

Ginekol Pol. 2013 Apr;84(4):293-7.

Inflammation and ovarian cancer–current views.

Kisielewski R1Tołwińska AMazurek ALaudański P.

 

Abstract

Ovarian cancers pose the greatest challenge for gynecological oncology. They are a heterogeneous, rapidly progressing and highly lethal group of malignancies and their etiology is still poorly understood. Among many hypotheses, explaining the pathogenesis of malignant tumors, chronic inflammation seems to play a significant role, which was proved in cervical, hepatic and esophageal cancers. The processes of inflammation and carcinogenesis are very much alike. Their similarity was experimentally confirmed by epidemiological, immunological, biochemical and genetic studies. Additionally this view is supported by indirect epidemiological and clinical evidence linking ovarian cancer with pelvic inflammatory disease, endometriosis or polycystic ovary syndrome. Chronic inflammation is a key factor in the pathogenesis of these illnesses. Moreover ovulation involving repeated damage and repair of the ovarian surface epithelium is in fact an inflammatory process. In this review, we focus on the role of inflammation in cancer initiation, promotion and progression with special emphasis on the ovarian cancer. We discuss the potential involvement of the fallopian tubes, endometriosis and microenvironment of tumors represented by cytokines, chemokines, growth factors and various enzymes that destroy the extracellular matrix. Considering that molecular biology is currently rapidly evolving, we focus on the function of the mammalian target of rapamycin (mTOR) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) in the pathophysiology of inflammation and cancer.

 

 

Int Surg. 2013 Apr-Jun;98(2):145-8.

Scar endometriosis in a patient with bladder exstrophy.

Kitajima T1Inoue MUchida KOtake KKusunoki M.

 

Abstract

Endometriosis is an ectopic occurrence of tissue morphologically and functionally resembling endometrial tissue in regions outside the uterine cavity. Although scar endometriosis after surgery has been shown to be most common among all the extrapelvic forms of endometriosis, endometriosis after bladder exstrophy surgery has not been reported, and here we present the first known case. A 26-year-old woman with a history of bladder exstrophy was aware of a painful induration at the operative scar located in the left lower abdominal wall, and presented at our hospital. Although the symptoms resolved, recurring exacerbation was observed after 9 months. Abdominal magnetic resonance imaging showed a heterogeneous mass 16 mm in diameter in the left abdominal wall with high signal intensity on T1W1 and T2W1 images. She underwent excisional biopsy of the lesion under general anesthesia. Histopathology confirmed the diagnosis of endometriosis. Eighteen months after surgery, she was well and free from recurrence.

 

 

Am J Obstet Gynecol. 2013 Sep;209(3):241.e1-9.

Prognostic analysis of endometrioid epithelial ovarian cancer with or without endometriosis: a 12-year cohort study of Chinese patients.

Wang S1Qiu LLang JHShen KHuang HFPan LYWu MYang JXGuo LN.

 

Abstract

OBJECTIVE:

Clinicopathological characteristics and possible prognostic factors among women with endometrioid epithelial ovarian cancer (EEOC) with or without concurrent endometriosis were investigated.

STUDY DESIGN:

A search of medical charts at Peking Union Medical College Hospital from 2000 through 2012 identified patients with EEOC with or without endometriosis.

RESULTS:

Of 188 patients with EEOC, concurrent endometriosis was identified in 32 (17.0%). Patients with concurrent endometriosis were approximately 5 years younger, more likely to be premenopausal, more likely to have an early stage of EEOC, and less likely to have high-grade tumors compared to those without endometriosis. The univariate analysis showed that concurrent endometriosis was a significant prognostic factor for disease-free survival, but this association did not remain in the multivariate analysis.

CONCLUSION:

Women with EEOC and concurrent endometriosis showed distinct characteristics and had longer disease-free survival when compared to those without endometriosis.

 

 

Hum Fertil (Camb). 2013 Sep;16(3):144-50

Controlled ovarian hyperstimulation regimens: a review of the available evidence for clinical practice. Produced on behalf of the BFS Policy and Practice Committee.

Nardo LG1Bosch ELambalk CBGelbaya TA.

 

Abstract

Before planning an assisted conception treatment cycle, a thorough assessment of the woman’s hormone profile and ovarian reserve is essential to aid the decision on the appropriate protocol for controlled ovarian hyperstimulation (COH). There is insufficient evidence to recommend the use of one type of gonadotrophins over another. There is no benefit of luteinising hormone (LH) supplementation in cycles stimulated with follicle stimulating hormone alone in an unselected population. There is some evidence to suggest a potential benefit of LH supplementation in patients with a history of poor ovarian response to stimulation and in those older than 35 years. The long gonadotrophin releasing hormone (GnRH) agonist protocol is the most widely used and is the preferred protocol in the unselected population of women undergoing COH for in vitro fertilisation or intra-cytoplasmic sperm injection. The GnRH antagonist protocol is best used for known or suspected high responders, including women with PCOS, as it reduces the risk of OHSS. There is a lack of robust evidence to suggest that the GnRH agonist protocol is better than the GnRH antagonist protocol in poor responders. The prolonged GnRH agonist protocol is advantageous in women who are undergoing COH due to pelvic endometriosis. Oral contraceptive pill pre-treatment adversely affects the IVF outcome in GnRH antagonist cycles, but not in GnRH agonist cycles.

 

 

 

Fertil Steril. 2013 Aug;100(2):568-77.

Constitutive and tumor necrosis factor-α-induced activation of nuclear factor-κB in adenomyosis and its inhibition by andrographolide.

Li B1Chen MLiu XGuo SW.

 

Abstract

OBJECTIVE:

To investigate the action of nuclear factor (NF)-κB in adenomyosis and evaluate the potential therapeutic effect of andrographolide on tumor necrosis factor (TNF)-α-induced expression of NF-κB-mediated genes cyclooxygease-2 (COX-2), vascular endothelial growth factor (VEGF), and tissue factor (TF) in adenomyotic stromal cells.

DESIGN:

Laboratory study using human tissues.

SETTING:

Academic hospital.

PATIENT(S):

Twenty-nine patients (cases) with histologically confirmed adenomyosis and 14 (controls) without adenomyosis or endometriosis.

INTERVENTION(S):

Endometrial stromal cells derived from tissue samples harvested from both cases and controls were subjected to electrophoretic mobility shift assay, and gene and protein expression analyses.

MAIN OUTCOME MEASURE(S):

The NF-κB DNA-binding activity and protein levels of NF-κB subunits p50 and p65 and the messenger RNA (mRNA) and protein levels of NF-κB-mediated genes COX-2, VEGF, and TF in cases and controls, and their changes after stimulation with TNF-α and treatment with andrographolide.

RESULT(S):

The constitutive NF-κB DNA-binding activity and protein expression levels of p50 and p65, and mRNA and protein levels of COX-2, VEGF, and TF in cases were significantly higher than that of controls. The binding activity level correlated positively with dysmenorrhea severity in cases. The TNF-α stimulation further increased the binding activity, and the mRNA and protein levels of COX-2, VEGF, and TF, but treatment with andrographolide significantly reduced them.

CONCLUSION(S):

NF-κB may be a pivotal transcription factor involved in the development of adenomyosis. Targeting NF-κB with inhibitors, like andrographolide, may hold promises of treating adenomyosis.

 

Fertil Steril. 2013 Aug;100(2):550-60.e3.

Fas ligand(+) fallopian tube epithelium induces apoptosis in both Fas receptor(+) T lymphocytes and endometrial cells.

Illanes SE1Maisey KSandoval MReyes FEFigueroa-Gaete CPérez-Sepúlveda ABusquets MGonzález PImarai M.

 

Abstract

OBJECTIVE:

To establish whether human fallopian tube (FT) epithelium can induce apoptosis in T lymphocytes and endometrial cells.

DESIGN:

Laboratory-based study.

SETTING:

Hospital.

PATIENT(S):

Women undergoing abdominal hysterectomy for FT samples, and women volunteers with and without endometriosis for endometrial biopsies.

INTERVENTION(S):

FT samples obtained at time of surgery performed in reproductive-aged women with normal menstrual cycles.

MAIN OUTCOME MEASURE(S):

T lymphocytes or endometrial cells coincubated with FT epithelial cells and assayed for apoptosis by DNA nick-end labeling and caspase-3 activity, with the presence of Fas ligand (FasL) and Fas receptor (FasR) assessed by indirect immunostaining.

RESULT(S):

The epithelium of the FT-induced apoptosis in T cells as well as in human endometrial cells. The mechanism probably involves the FasL/FasR system; accordingly, we observed FasL at the apical surface of the epithelium and in the stroma of the FT at all phases of the menstrual cycle except during the early proliferative phase. The endometrial samples from patients with endometriosis did not express FasR and were resistant to apoptosis.

CONCLUSION(S):

In both FasR(+) T lymphocytes and endometrial cells, FasL(+) FT cells induce apoptosis. Data suggest that the FT epithelium acts as a barrier to limit the influx of lymphocytes as well as endometrial cells ascending the tube. Failure of these regulatory mechanisms may be related to the development of endometriosis.

Pain. 2013 Aug;154(8):1318-24.

Reflex receptive fields are enlarged in patients with musculoskeletal low back and neck pain.

Biurrun Manresa JA1Neziri AYCuratolo MArendt-Nielsen LAndersen OK.

 

Abstract

Pain hypersensitivity has been consistently detected in chronic pain conditions, but the underlying mechanisms are difficult to investigate in humans and thus poorly understood. Patients with endometriosis pain display enlarged reflex receptive fields (RRF), providing a new perspective in the identification of possible mechanisms behind hypersensitivity states in humans. The primary hypothesis of this study was that RRF are enlarged in patients with musculoskeletal pain. Secondary study end points were subjective pain thresholds and nociceptive withdrawal reflex (NWR) thresholds after single and repeated (temporal summation) electrical stimulation. Forty chronic neck pain patients, 40 chronic low back pain patients, and 24 acute low back pain patients were tested. Electrical stimuli were applied to 10 sites on the sole of the foot to quantify the RRF, defined as the area of the foot from where a reflex was evoked. For the secondary end points, electrical stimuli were applied to the cutaneous innervation area of the sural nerve. All patient groups presented enlarged RRF areas compared to pain-free volunteers (P<.001). Moreover, they also displayed lower NWR and pain thresholds to single and repeated electrical stimulation (P<.001). These results demonstrate that musculoskeletal pain conditions are characterized by enlarged RRF, lowered NWR and pain thresholds, and facilitated temporal summation, most likely caused by widespread spinal hyperexcitability. This study contributes to a better understanding of the mechanisms underlying these pain conditions, and it supports the use of the RRF and NWR as objective biomarkers for pain hypersensitivity in clinical and experimental pain research.

 

 

 

Dig Liver Dis. 2013 Oct;45(10):816-9

Ultrasound-guided percutaneous biopsy for diagnosis of gastrointestinal lesions.

de Sio I1Funaro AVitale LMNiosi MFrancica GFederico ASgambato DLoguercio CRomano M.

 

Abstract

BACKGROUND AND AIMS:

Endoscopical examination is not always sufficient for the diagnosis of gastrointestinal masses. This study assessed the diagnostic accuracy and safety of ultrasound-guided percutaneous biopsy of gastrointestinal lesions.

METHODS:

This retrospective study evaluated 114 patients who underwent ultrasound-guided biopsy of gastrointestinal masses with a 18G needle. Thirty-two of these patients underwent a 22G fine-needle biopsy for cytology. Histology was compared with a composite standard of reference for diagnosis (i.e. post-surgery histological evaluation in 73 cases and computed tomography or magnetic resonance scan findings, together with a compatible clinical follow-up for at least 24 months, in the remaining 41 cases). Safety was assessed by recording side effects for up to 4h after the procedure.

RESULTS:

Of the 114 lesions evaluated, 112 were malignant (98.2%) and 2 benign (1.8%). Specimens were adequate for histology in all but one case. Specimens were obtained from the stomach (n=38; 33.3%), small bowel (n=36; 31.6%) and colon (n=40; 35.1%). Diagnosis was correct in 113/114 cases (99.1%). Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 99.1%, 100%, 100%, 66%, and 99%, respectively. One of the 114 patients (0.9%) bled from a gastric GIST.

CONCLUSIONS:

Ultrasound-guided percutaneous biopsy of gastrointestinal lesions is a valid alternative when diagnosis of a gastrointestinal mass cannot be obtained with an endoscopical procedure.

 

 

Am J Obstet Gynecol. 2013 Aug;209(2):106.e1-10.

A metaanalysis on alcohol consumption and risk of endometriosis.

Parazzini F1Cipriani SBravi FPelucchi CChiaffarino FRicci EViganò P.

 

Abstract

OBJECTIVE:

To offer a general figure of the available data on the relation between alcohol intake and risk of endometriosis, we conducted a systematic review and a metaanalysis of studies published up to May 2012.

STUDY DESIGN:

We carried out a literature search of all case-control and cohort studies published as original articles in English up to May 2012. Only those papers that were published as full-length articles were considered. Pooled estimates of the relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated using fixed or, when significant heterogeneity among estimates emerged, random effects models. A total of 15 studies were identified for the review.

RESULTS:

The summary estimate was 1.24 (95% CI, 1.12-1.36) for any alcohol intake vs no alcohol intake. Considering the results of the analyses of infrequent, moderate/regular, and heavy alcohol intake vs no alcohol intake, the summary RR estimates were, respectively, 1.14 (95% CI, 0.86-1.52), 1.23 (95% CI, 1.08-1.40), and 1.19 (95% CI, 0.99-1.43). Three studies reported separate results for current and former drinkers, and the summary RR were 1.42 (95% CI, 1.14-1.76) and 1.09 (95% CI, 0.83-1.43), respectively.

CONCLUSION:

The present metaanalysis provides evidence for an association between alcohol consumption and endometriosis risk. Further studies are needed to clarify whether alcohol consumption may exacerbate an existing disease or could be related to the severity of the disease.

 

 

Yonsei Med J. 2013 Jul;54(4):921-6.

Preoperative serum anti-mullerian hormone level in women with ovarian endometrioma and mature cystic teratoma.

Kim JY1Jee BCSuh CSKim SH.

 

Abstract

PURPOSE:

To investigate whether preoperative serum anti-mullerian hormone (AMH) levels are lower in women with ovarian endometrioma and in women with mature cystic teratoma of the ovaries.

MATERIALS AND METHODS:

In a tertiary university hospital, a retrospective case-control study was performed. Serum AMH levels between an advanced (stage III and IV) endometrioma group (n=102) and an age- and body mass index (BMI)-matched control group were compared. Serum AMH levels between an ovarian mature cystic teratoma group (n=48) and age- and BMI-matched controls were also compared.

RESULTS:

Absolute serum AMH and multiples of the median for AMH (AMH-MoM) relevant to Korean standards were lower in the endometrioma group than controls, but this was not statistically significant (mean±SEM, 2.9±0.3 ng/mL vs. 3.3±0.3 ng/mL, p=0.28 and 1.3±0.1 vs. 1.6±0.1, p=0.29, respectively). Specifically, the stage IV endometriosis group (n=51) exhibited significantly lower serum AMH and AMH-MoM (2.1±0.3 vs. 3.1±0.4 ng/mL, p=0.02 and 1.1±0.1 vs. 1.7±0.2, p=0.03, respectively). Serum AMH and AMH-MoM levels were similar between stage III endometriosis and controls (3.7±0.5 vs. 3.4±0.5 ng/mL and 1.6±0.2 vs. 1.5±0.2, respectively), as well as between the mature cystic teratoma group and controls (4.0±0.5 ng/mL vs. 4.0±0.5 ng/mL and 1.6±0.2 vs. 1.6±0.3, respectively). Interestingly, AMH-MoM level was negatively correlated with endometriosis score with statistical significance (r²=0.13, p<0.01).

CONCLUSION:

In women with advanced ovarian endometrioma, preoperative serum AMH values tended to be lower than those for age and BMI-matched controls. Notably, stage IV endometrioma appeared to be closely associated with decreased ovarian reserve, even before operation. Clinicians should keep this information in mind before undertaking surgery of ovarian endometrioma.

 

 

Case Rep Obstet Gynecol. 2013;2013:202458

A case of extrauterine endometrial stromal sarcoma in the colon diagnosed three decades after hysterectomy for benign disease.

Ayuso A1Fadare OKhabele D.

 

Abstract

Extrauterine endometrial stromal sarcoma (ESS) is rare and typified by delayed recurrence of primary ESS. Here, we report an unusual case of colonic ESS in a woman with a remote history of hysterectomy. An 80-year-old woman, with a history of hysterectomy and bilateral salpingo-oophorectomy for abnormal bleeding and endometriosis 37 years prior to presentation, was diagnosed with ESS in the colon. She was treated with laparoscopic low anterior resection, followed by megestrol acetate, and has been in remission for more than 4 years. This case highlights the rarity of extra-uterine ESS in the colon, especially in the absence of a known history of primary uterine ESS. The patient’s history of endometriosis may have been a predisposing risk factor. ESS in the colon may be treated successfully with surgical resection and progestin therapy. Indefinite surveillance is recommended to monitor for late recurrences.

 

 

Case Rep Obstet Gynecol. 2013;2013:837903

Spontaneous healing of a rectovaginal fistula developing after laparoscopic segmental bowel resection for intestinal deep infiltrating endometriosis.

Kondo W1Ribeiro RTrippia CHZomer MT.

 

Abstract

The surgical treatment of intestinal deep infiltrating endometriosis has an associated risk of major complications such as dehiscence of the intestinal anastomosis, pelvic abscess, and rectovaginal fistula. The management of postoperative rectovaginal fistula frequently requires a reoperation and the construction of a stoma for temporary fecal diversion. In this paper we describe a 27-year-old woman undergoing laparoscopic treatment of deep infiltrating endometriosis (extramucosal cystectomy, resection of the uterosacral ligaments, resection of the posterior vaginal fornix, and segmental bowel resection) complicated by a rectovaginal fistula, which healed spontaneously with nonsurgical conservative treatment.

 

 

Case Rep Surg. 2013;2013:714126.

Endometrioid adenocarcinoma of caecum causing intussusception.

Verma R1Osborn SHorgan K.

 

Abstract

Malignant transformation of endometriosis is rare and is usually seen in ovarian endometriosis. The colon and rectum are the most common sites for extragonadal endometriosis, and although serosal involvement is commonly seen, mucosal involvement is rare. Malignant transformation of endometriosis is a rare but a well-known complication of endometriosis. We report an unusual presentation of endometrioid adenocarcinoma with lymph node metastasis, arising from endometriosis in the caecal wall and causing ileocaecal intussusception. The patient presented with sudden onset of abdominal pain with features suggestive of acute appendicitis. Diagnostic laparoscopy revealed an ileocaecal intussusception. Conversion to open surgery confirmed a caecal mass causing ileocaecal intussusception, and a radical right hemicolectomy was performed. Histology revealed endometrioid adenocarcinoma arising in a focus of endometriosis in the muscularis propria and involving the mucosa, with one regional metastatic lymph node.

 

 

Ceska Gynekol. 2013 Apr;78(2):175-81.

Selective progesterone receptor modulators and their therapeutical use.

Driák D1Sehnal BSvandová I.

 

Abstract

Currently developed selective progesterone receptor modulators (SPRMs) are steroid derived compounds with a bulky radical substitution at carbon 11. They interact with progesterone receptor and exert antagonistic or/and agonistic effects. Mifepristone was approved for pregnancy termination and ulipristal acetate as emergency contraception and pharmacological therapy of uterine fibroids. SPRMs inhibit endometrial proliferation and myoma growth, this suggests a therapeutical effect in cases of endometriosis and other estrogen-dependent diseases.

 

 

Arch Gynecol Obstet. 2013 Dec;288(6):1301-8.

The effects of levamisole on experimental endometriosis: a randomized controlled trial in a rat model.

Azimirad A1Alborzi SKumar PVZarei AAzimirad M.

 

Abstract

PURPOSE:

To assess the effects of levamisole on experimental endometriosis in rats through the histopathology of the implants, the blood leukocyte and lymphocyte counts and the concentrations of interleukin-6, vascular endothelial growth factor-A and tumor necrosis factor-alpha in the peritoneal environment at the three healthy, endometriotic and post-treatment milestones.

METHODS:

Twenty-two 8-week-old Sprague-Dawley rats with normal estrus cycles were recruited in a prospective, parallel-group, placebo-controlled, double-blind, stratified-randomized animal trial with the equal allocation ratio of 1:1 challenging the efficacy of levamisole. Endometriosis was induced. After 6 weeks, laparotomy was performed to randomly excise one implant for histopathology assessment. Based on the results, they were stratified randomized and allocated (by software) to two groups of nine: levamisole (5 mg/rat/day) or placebo. After 6 weeks, necropsy was done. Two days before each laparotomy, blood samples and during the procedure, peritoneal wash were collected for ELISA.

RESULTS:

Seven rats showed success in treatment in the levamisole group, while three did in the other group. The histopathology results descriptively revealed a drop in the levamisole group, which was not meaningful statistically (0.66 ± 1.32 vs. 2.00 ± 1.50, p = 0.065). The comparisons of the post-treatment leukocytes and lymphocytes in the groups showed significant differences (11088.88 ± 5869.50 vs. 4677.77 ± 3476.98, p = 0.008, and 8588.88 ± 5721.32 vs. 3511.11 ± 2835.24, p = 0.014, respectively). The results of the cytokines were mostly, but not completely, in favor of the efficacy of levamisole.

CONCLUSION:

This study indicates a possible successful role for levamisole in the treatment of experimental endometriosis. Further studies to assess the effects of high dose levamisole on endometriosis are recommended.

 

 

Biomedica. 2012 Oct-Dec;32(4):570-7.

Influence of CYP3A4/5 polymorphisms in the pharmacokinetics of levonorgestrel: a pilot study.

Moreno I1Quiñones LCatalán JMiranda CRoco ÁSasso JTamayo ECáceres DTchernitchin ANGaete LSaavedra I.

 

Abstract

INTRODUCTION:

Levonorgestrel a synthetic progestagen used for endometriosis, dysmenorrhea and emergency contraception, is quickly and completely absorbed in the digestive tract. levonorgestrel is predominantly metabolised through hepatic routes that utilise the CYP3A system (CYP3A4 and CYP3A5).

OBJECTIVE:

This study aimed to evaluate the association between variant alleles of CYP3A4*1B and CYP3A5*3 polymorphisms and the pharmacokinetics of levonorgestrel.

MATERIALS AND METHODS:

A group of 17 adult female healthy volunteers who signed an informed consent were genotyped for CYP3A4 and CYP3A5 through PCR-RFLP. Volunteers were submitted to pharmacokinetic analysis where, after a 12-hour overnight fast, they received a single oral dose of 0.75 mg of levonorgestrel. Serial blood samples were obtained (0 to 24 hours), and levonorgestrel concentrations were determined by UPLC-MS/MS to determine pharmacokinetic parameters. The procedures employed herein were performed according to the Declaration of Helsinki and Good Clinical Practices standards.

RESULTS:

Observed genotype frequencies in the studied group for CYP3A4*1B were 11.8% for *1B/*1B, 5.8% for *1/*1B and 82.4% for *1/*1. CYP3A5*3 frequencies were 70.5% for *3/*3, 23.5% for *1/*3 and 6.5% for *1/*1. A high pharmacokinetic variability between volunteers was observed, but no statistical association of pharmacokinetic parameters was found within the studied CYP3A4/5 polymorphisms.

CONCLUSIONS:

Genetic polymorphisms could be important factors in determining inter-patient variability in plasma levonorgestrel concentrations, which in this study were not significantly associated with the presence of CYP3A4*1B and CYP3A5*3 polymorphisms. Therefore, due to the significant inter-patient variability that we observed during the course of this study, it is necessary to carry out studies with larger number of volunteers.

 

 

 

 

J Ultrasound Med. 2013 Jun;32(6):931-5

Three-dimensional sonography for diagnosis of rectovaginal septum endometriosis: interobserver agreement.

Pascual MA1Guerriero SHereter LBarri-Soldevila PAjossa SGraupera BRodriguez I.

 

Abstract

OBJECTIVES:

The aim of this study was to evaluate the interobserver agreement for diagnosis of deep endometriosis of the rectovaginal septum using introital 3-dimensional (3D) sonography.

METHODS:

Two experienced observers (observers A and B) performed a retrospective review of stored 3D sonographic volumes from a sample of 84 consecutive patients with a clinical suspicion of endometriosis. Each observer, independently and blinded to each other, evaluated the presence or absence of involvement of the rectovaginal septum. When no lesion was seen, the observers were asked to judge whether the acquisition of the volume was suboptimal for interpretation or whether no lesion on the rectovaginal septum was detectable. One inadequate acquisition case was discarded; a total of 83 cases were evaluated. To calculate the performance of introital 3D sonography, 7 discordant cases were reviewed by a third observer. Interobserver agreement was assessed by calculating the κ index, and the sensitivity, specificity, positive predictive value, and negative predictive value for the 3 observers were also determined.

RESULTS:

Interobserver agreement was 0.816 (95% confidence interval, 0.69-0.93), representing very good agreement. Sensitivity was 74.1%; specificity, 85.7%; positive predictive value, 71.4%; and negative predictive value, 87.3%.

CONCLUSIONS:

Our results show that introital 3D sonography for diagnosis of deep endometriosis of the rectovaginal septum is reproducible, with very good interobserver agreement.

 

 

 

J Obstet Gynaecol Res. 2013 Jul;39(7):1253-8.

Effect of vitamin C on the growth of experimentally induced endometriotic cysts.

Durak Y1Kokcu AKefeli MBildircin DÇelik HAlper T.

 

Abstract

AIM:

The aim of this study was to investigate the effect of vitamin C on the growth of experimental endometriotic cysts.

MATERIAL AND METHODS:

The endometrium of the uterine horn wall (diameter, 4 mm) was implanted onto the inner surface of the anterior abdominal wall of 40 Wistar albino adult female rats, by laparotomy. The day after the implantation, the rats were randomly assigned into four groups (control group and experimental groups [V1, V2, and V3]) comprising 10 rats each. For 6 weeks, the control group (Group C) received 1 mL distilled water, whereas the experimental groups (Groups V1, V2, and V3) received 0.5 mg, 1.25 mg, and 2.5 mg of vitamin C in 1 mL of distilled water, respectively. The doses were given via oral gavage once per day. At the end of the administration, a second laparotomy was performed and endometriotic cyst volumes and weights of rats among the groups were compared. In addition, the stromal and glandular tissue and the natural killer cell contents of the cysts were compared among the groups.

RESULTS:

The cyst volume in Group V3 and the cyst weights in Groups V2 and V3 were significantly lower than those in Group C. The natural killer cell content in Groups V1, V2, and V3 was significantly lower than that in Group C. Stromal and glandular tissue contents of the groups were not significantly different.

CONCLUSIONS:

The dose-dependent vitamin C supplementation significantly reduced the volumes and weights of the endometriotic cysts.

 

 

Reprod Sci. 2013 Nov;20(11):1339-48.

A novel pilot study of endometrial stromal cells and immune cell populations in sentinel uterine-draining lymph nodes during the menstrual cycle and in endometriosis.

Berbic M1Ng CHBlack KMarkham RRussell PBasten AFraser ISHey-Cunningham AJ.

 

Abstract

Recent studies suggest that changes in certain uterine immune cell populations in endometrium of women with endometriosis are likely to precede changes at ectopic sites. This preliminary study is a first look into the function of uterine-draining lymph nodes (LNs) during the menstrual cycle and in the presence of endometriosis. Paraffin-embedded obturator LNs were obtained from women with (n = 7, mean age 44.3) and without (n = 9, mean age 38.4) endometriosis, who had undergone hysterectomy for cervical or ovarian cancer and in whom LN involvement was not detected. Immunohistochemical staining for endometrial stromal cells and a range of immune cell populations was performed. The CD10+ endometrial stromal cells were detected in uterine-draining LNs throughout the menstrual cycle with numbers peaking during menstruation. The inflammatory process of menstruation was also associated with increased numbers of CD3+, CD4+, Foxp3+, DC-Sign+, CD68+, CD20+, CD79+, and plasma cells. In endometriosis, CD10+ endometrial stromal cells were further increased in numbers, but CD3+, CD4+, DC-Lamp+, FoxP3+, and plasma cells were reduced. This study indicates that efficient immunological responses may be required to contain shed endometrial fragments within the draining uterine LNs thus preventing their further dissemination with establishment of ectopic lesions at distant sites.

 

 

Hum Reprod Update. 2013 Sep-Oct;19(5):558-69.

The role of the peritoneum in the pathogenesis of endometriosis.

Young VJ1Brown JKSaunders PTHorne AW.

 

Abstract

BACKGROUND Endometriosis affects 6-10% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhoea, dyspareunia and infertility. Endometriosis is defined by the presence of endometrial tissue outside the uterus, most commonly attached to the pelvic peritoneum. The endometrium in women with endometriosis is reported to be altered and there is increasing evidence that the phenotype of the pelvic peritoneum may also play a role in the establishment and maintenance of the disease. The aim of this review is to discuss the putative role of the pelvic peritoneum in the pathophysiology of peritoneal endometriosis. METHODS A review was undertaken of the published literature on (i) the anatomy and physiology of the peritoneum and (ii) the potential roles played by peritoneal cells in the establishment and maintenance of peritoneal endometriosis. The current understanding of the biology of peritoneal endometriosis is summarized and the potential interaction of the peritoneum with ectopic endometrial cells in endometriosis is highlighted. RESULTS Several studies indicate that differential expression of peritoneal mesothelial adhesion factors occurs in women with endometriosis, providing potential ectopic endometrial cell attachment sites for the establishment of endometriosis lesions. Changes in the peritoneal mesothelial cell phenotype, including loss of tight junctions, may allow ectopic cells to bind to, or early lesions to invade into, the extracellular matrix. Epithelial-to-mesenchymal transition of peritoneal mesothelial cells may also lead to an increase in lesion invasion and formation of fibrotic tissue in and around the lesion. There is evidence that the peritoneal mesothelium may also play a role in the invasion potential of ectopic cells by production of MMPs increasing local tissue remodelling. Peritoneal immune scavenging function may be lowered in women with endometriosis; for example there is a notable increase in macrophage-derived secretion products in women with endometriosis associated with increases in cell proliferation, cell adhesion and neovascularization. CONCLUSIONS The pelvic peritoneum appears to play a key role in the development and maintenance of endometriosis.

 

 

Balkan Med J. 2013 Jun;30(2):155-60

Abdominal wall endometrioma: ultrasonographic features and correlation with clinical findings.

Solak A1Genç B1Yalaz S2Sahin N1Sezer TÖ3Solak I3.

 

Abstract

BACKGROUND:

The diagnosis of abdominal wall endometrioma (AWE) is often confused with other surgical conditions. Certain factors relating to knowledge of the clinical history of the disease make correct diagnosis and treatment difficult.

AIMS:

To present the clinical findings and ultrasonographic (US) features of AWE with special emphasis on size-related features.

STUDY DESIGN:

This study reviewed abdominal wall endometriomas during a 2-year period in the Radiology Department of Sifa University Hospital, Izmir.

METHODS:

Eleven women (mean age 32.6 years) with 12 scar endometriomas (mean diameter 29.2 mm) were consecutively evaluated by US and Colour Doppler examination (CDUS) prior to surgery. Lesions were grouped into large (≥3 cm) and small nodules. Vascularisation was classified as location (central, peripheral and mixed) and severity (absent, moderately vascular and hypervascular). In each patient, the nature of pain (absent, cyclic: associated with menstruation and continuous), historical and clinical data were documented. Four patients underwent Magnetic Resonance Imaging and their findings were presented. Fisher’s exact test, χ(2) test for categorical data and the unpaired T-test for continuous variables were used for statistical analysis.

RESULTS:

In all the women, US of the AWE showed the presence of a solid hypoechoic mass (less echogenic than the surrounding hyperechoic fat) within the abdominal wall. There was a significant correlation between AWE sizes with repeated caesareans and the mean time between the last operation and admission to hospital (p<0.05). Large endometriomas showed increased central vascularity (p<0.05). Cyclic pain was more frequent in small lesions, whereas continuous pain was more commonly found in patients with larger lesions (p<0.05).

CONCLUSION:

AWE is often misdiagnosed clinically because endometriosis may occur years after the caesarean section, the pain is often non-cyclic in nature, and there is not always a palpable tender mass. The sonographic and Doppler findings, along with proper correlation with clinical data, may substantially contribute to the correct diagnosis of endometrioma.

 

 

Dev Reprod. 2013 Jun;17(2):133-40

Cathepsin B in eutopic and ectopic endometrial tissues of patients with endometriosis.

Kim CH1Lee YJ1Kim JB1Lee YJ1Ahn JW2Kim SH1Chae HD1Kang BM1.

 

Abstract

This study was performed to investigate the expression of cathepsin B mRNA and protein in eutopic and ectopic endometrial tissues of patients with endometriosis and in normal endometrial tissues and to clarify the association between the cathepsin B expression and endometriosis. A total of 40 women with histologically confirmed endometriosis were recruited for study group. For controls, 20 women undergoing operative treatment for uterine myoma, cervical intraepithelial neoplasia (CIN) or benign gynecologic conditions other than endometriosis were recruited. Eutopic endometrial tissues of both groups and ectopic endometrial tissue of study group were collected during the operations. We employed real time reverse transcriptase – polymerase chain reaction (RT-PCR) to quantify mRNA levels of cathepsin B in these tissues. Then, we performed western blot analysis to measure the protein levels of cathepsin B. The expressions of cathepsin B mRNA and protein were significantly higher in both eutopic and ectopic endometrial tissues of women with endometriosis than in endometrial tissues of controls. These data suggest that the higher expression of cathepsin B in the endometrial tissues might be associated with the development of endometriosis. In addition, eutopic endometrium itself with higher expression cathepsin B may play a pivotal role in the histogenesis of endometriosis.

 

 

 

J Robot Surg. 2013 Jun;7(2):163-9.

Retrospective analysis of robot-assisted versus standard laparoscopy in the treatment of pelvic pain indicative of endometriosis.

Dulemba JF1Pelzel C2Hubert HB3.

 

Abstract

We examined the feasibility of treating pelvic pain in patients with suspected endometriosis using robot-assisted laparoscopic techniques compared with CO2 laser laparoscopy, in a retrospective review from a single surgeon’s practice, including the last 100 standard laparoscopic (December 2004-September 2007) and the first 180 robot-assisted (July 2007-January 2010) surgeries to treat suspected endometriosis. Perioperative outcomes and postoperative pain were compared by technique. Patients in each group were comparable in gravidity, body mass index, prior endometriosis, prior abdominopelvic surgery, American Fertility Society stage, and biopsy rates. Operative time (77 vs. 72 min), blood loss (29 vs. 25 mL), and complication rates (1.1 vs. 0 %) in robot-assisted and standard laparoscopy were low and similar for both approaches. Differences were apparent in biopsies confirming endometriosis (80 % robot-assisted vs. 56.8 % traditional laparoscopy, p < 0.001). Most patients reported improved postoperative pain at the first follow-up visit with no differences between the surgical approaches (85 % vs. 80 %, p = 0.365). Perioperative outcomes with robot-assisted surgery were comparable to outcomes using CO2 laser laparoscopy. Further investigation is needed to ascertain whether robotics provides better visual acuity and excision of endometriosis, as suggested by these data, and if long-term resolution of symptoms and fertility outcomes differ by surgical approach.

 

 

J Anal At Spectrom. 2013 Jun;28(6):821-830.

Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry.

Steuerwald AJ1Parsons PJ1Arnason JG1Chen Z2Peterson CM3Louis GM2.

 

Abstract

Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e.g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n=619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including 74Se, 76Se, 77Se, 78Se, 80Se, and 82Se. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens.

 

 

Fertil Steril. 2013 Sep;100(3):761-9.

Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.

Delbandi AA1Mahmoudi MShervin AAkbari EJeddi-Tehrani MSankian MKazemnejad SZarnani AH.

 

Abstract

OBJECTIVE:

To study immunophenotype, differential proliferation capacity, invasiveness, adhesion, and cytokine production in ectopic and eutopic endometrial stromal cells (EESCs and EuESCs) from patients with endometriosis.

DESIGN:

In vitro study.

SETTING:

Academic research center.

PATIENT(S):

Patients with ovarian endometriosis (endometrioma) and nonendometriotic controls.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

EESCs and EuESCs from 25 patients with endometrioma and ESCs from 20 nonendometriotic controls (CESCs) were isolated, and their immunophenotype, proliferation, invasion, adhesion, and cytokine production were assessed and compared.

RESULT(S):

Isolated ESCs from all three sources expressed markers specific for cells of mesenchymal origin but were negative for hematopoietic markers. EESCs exhibited a significantly lower proliferation rate in fibronectin-coated plates and less invasive capacity compared with CESCs or EuESCs. Among all stromal cell groups studied, EuESCs showed the highest invasive behavior. EESCs adhered more firmly to extracellular matrix than EuESCs or CESCs in all time intervals examined. The levels of interleukin (IL) -6 and IL-8 production by EESCs were significantly higher compared with those of EuESCs or CESCs.

CONCLUSION(S):

The results of the present study demonstrated that retrograde menstruation alone does not account for the pathogenesis of endometriosis as eutopic and ectopic counterparts of ESCs from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.

 

 

Mol Hum Reprod. 2013 Oct;19(10):644-54.

Genetic association studies in female reproduction: from candidate-gene approaches to genome-wide mapping.

Zhao H1Chen ZJ.

 

Abstract

Many genetic association studies have been performed to investigate disorders of female reproduction, such as polycystic ovary syndrome, premature ovarian failure and endometriosis. These disorders typically manifest heterogeneously, and their pathogeneses are influenced by polygenic and environmental factors. Researchers evaluating these genetic associations have chosen candidate genes related to hormone action, steroid biosynthesis, inflammatory cytokines and autoimmune factors. Several of these genes have yielded statistically significant associations with female reproductive disorders; however, few associations have been robust and reproducible. Whole-genome association studies generate more reliable and unbiased results and represent a breakthrough in genetic studies of female reproduction. Nevertheless, to date only a very small fraction of the overall heritability has been identified and so further studies are needed.

 

 

 

Clin Exp Obstet Gynecol. 2013;40(1):40-4.

Frequency of endometriosis and adenomyosis in patients with leiomyomas, gynecologic premalignant, and malignant neoplasias.

Nomelini RS1Ferreira FABorges RCAdad SJMurta EF.

 

AbstracT

OBJECTIVE:

This study investigated the association between gynecological neoplasms, endometriosis, and adenomyosis in women who underwent surgical treatment for gynecological cancer and uterine leiomyoma during reproductive years or after menopause.

MATERIALS AND METHODS:

Information was collected from patient records from the Hospital’s database from 1985 to 2007. The study included 502 women, of which 375 were premenopausal and 132 were postmenopausal.

RESULTS:

A significant association was observed between the occurrence of adenomyosis in cancer in women with four or more pregnancies, and in women aged over 40 years (p < 0.0001). The frequency of adenomyosis was significantly higher than the frequency of endometriosis for cancer in two sites (p = 0.0419) or for leiomyomas (p < 0.0001).

CONCLUSION:

Therefore adenomyosis is more frequently found than endometriosis in women with leiomyomas or cancer in two sites in premenopausal women, and clinicians need to be aware of patients with adenomyosis and the risk of cancer.

 

 

Clin Exp Obstet Gynecol. 2013;40(1):95-7.

The value of negative Chlamydia trachomatis antibody in prediction of normal tubes in infertile women.

Raoofi Z1Barchinegad MHaghighi L.

 

Abstract

OBJECTIVE:

To evaluate the value of Chlamydia trachomatis antibody testing in prediction of at least one normal tube in infertile women.

MATERIALS AND METHODS:

Eighty infertile women without any history of abdominal or pelvic surgery, pelvic inflammatory disease, and endometriosis were recruited in this cross-sectional study from 2009 to 2010. The patients underwent hysterosalpingography, laparoscopy, and anti Chlamydia trachomatis IgG antibody (CAT) testing. We compared laparoscopy findings and CAT regarding sensitivity, specificity, accuracy, and predicting value of tubal conditions.

RESULTS:

The CAT was positive in 50 patients (62.5%) and laparoscopy was positive in 32 patients (40%). The CAT was significantly higher in women with tubal disease (1.88 +/- 0.34) versus in women with normal tubes (1.21 +/- 0.28) (p = 0.003). Five out of 30 sero-negative women had unilateral tubal abnormality and none of them had bilateral tubal obstruction or severe pelvic adhesion. The sensitivity, specificity, positive and negative predictive value, and accuracy of the CAT in prediction of one normal tube were 100%, 42.25%, 18%, 100%, and 48.75%, respectively.

CONCLUSION:

The negative predictive value of CAT to predict at least one normal tube in infertile women without history of abdominal or pelvic surgery, pelvic inflammatory disease, and endometriosis was 100%.

 

 

Gynecol Oncol. 2013 Sep;130(3):629-33.

Anti-HE4 antibodies in infertile women and women with ovarian cancer.

Hellstrom I1Swisher EHellstrom KEYip YYAgnew KLuborsky JL.

 

Abstract

OBJECTIVES:

To develop an assay for anti-HE4 antibodies and assess such antibodies in sera from women with increased epidemiologic risk for ovarian cancer (infertility) and patients with ovarian cancer in comparison to controls.

METHODS:

An ELISA was developed to measure antibodies to recombinant full length HE4 and cut-off values were determined for different levels of specificity (up to 99%).

RESULTS:

Infertile women more frequently had anti-HE4 antibodies than controls (23% at 98% specificity, p < 0.001) with antibodies most frequent in women with POF (31%) and ovulatory dysfunction (47%). There was also an increased frequency of anti-HE4 antibodies in patients with ovarian cancer (14% at 97% specificity, p < 0.01), but more women with certain types of infertility have anti-HE4 antibodies than women with ovarian cancer. Most patients with ovarian cancer have circulating HE4 antigen, which may interfere with detection of antibodies, while the level of HE4 antigen in sera from infertile women was not higher than in normal controls. There was a statistically significant correlation between antibodies to HE4 and antibodies to mesothelin in the same patients.

CONCLUSIONS:

Women with certain types of infertility, which have increased risk to develop ovarian cancer, and women with ovarian cancer more frequently than controls have antibodies to HE4, a biomarker for ovarian cancer. The antibodies may reflect a tumor-promoting Th2 type of inflammation.

 

 

Arch Pediatr. 2013 Aug;20(8):910-4.

Meno-metrorrhagia, dysmenorrhea in adolescents.

Bricaire L1Laroche EChristin-Maitre S.

 

Abstract

Menometrorrhagia is a common symptom in adolescents. It is idiopathic in most cases. In case of menometrorrhagia, it is necessary to exclude a pregnancy, a disorder of hemostasis, particularly the von Willebrand disease, as it represents the most common inherited disorder, and more rarely a chronic disease or an endocrinopathy. History of the bleedings, menstrual blood loss quantification by the Higham score and tolerance of the bleedings (blood pressure) should be evaluated. Laboratory testing includes hCG, ferritin level, a complete blood count, a prothrombin time, an activated partial thromboplastin. Management of menometrorrhagia is related to the severity of the blood loss. It associates antifibrinolytics or non-steroidal anti-inflammatory agents (NSAIDS) with hormonal treatments, such as estrogen-progestin oral contraceptive pill or cyclic oral progestins. Primary or functional dysmenorrhea concerns 40 to 90% of the teenagers and represents a frequent cause of school absenteeism. Management of primary dysmenorrhea is primarily based on a treatment by NSAIDS. In case of its inefficacy or if contraception is needed hormonal treatments, such as estrogen-progestin combined pill should be prescribed. It is very important when pelvic pain is chronic and not soothed by simple medications to look for a secondary dysmenorrhea, mainly endometriosis. In such cases, pelvic magnetic resonance imaging should be performed.

 

 

 

 

Hum Reprod Update. 2013 Sep-Oct;19(5):570-82

Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review.

Janssen EB1Rijkers ACHoppenbrouwers KMeuleman CD’Hooghe TM.

 

Abstract

BACKGROUND Endometriosis associated with pain symptoms in adolescents has been extensively reported, but the exact prevalence is unclear because pain symptoms may be atypical and endometriosis can only be diagnosed by laparoscopy. The aim of this paper is to provide a systematic review of the prevalence of endometriosis diagnosed by laparoscopy in adolescents. METHODS A systematic literature search was carried out for relevant articles published between 1980 and 2011 in the databases PUBMED and EMBASE, based on the keywords ‘endometriosis’, ‘laparoscopy’, ‘adolescents’ and ‘chronic pelvic pain (CPP)’. In addition, the reference lists of the selected articles were examined. RESULTS Based on 15 selected studies, the overall prevalence of visually confirmed endometriosis was 62% (543/880; range 25-100%) in all adolescent girls undergoing laparoscopic investigation, 75% (237/314) in girls with CPP resistant to treatment, 70% (102/146) in girls with dysmenorrhea and 49% (204/420) in girls with CPP that is not necessarily resistant to treatment. Among the adolescent girls with endometriosis, the overall prevalence of American Society of Reproductive Medicine classified moderate-severe endometriosis was 32% (82/259) in all girls, 16% (17/108) in girls with CPP resistant to treatment, 29% (21/74) in girls with dysmenorrhea and 57% (44/77) in girls with CPP that is not necessarily resistant to treatment. Due to the quality of the included papers an overestimation of the prevalence and/or severity of endometriosis is possible. CONCLUSIONS About two-thirds of adolescent girls with CPP or dysmenorrhea have laparoscopic evidence of endometriosis. About one-third of these adolescents with endometriosis have moderate-severe disease. The value of early detection of endometriosis in symptomatic adolescents and the indications for laparoscopic investigation in adolescents require more research.

 

 

 

Middle East Fertil Soc J. 2012 Dec 1;17(4):221-225.

Pain and endometriosis: Etiology, impact, and therapeutics.

Taylor RN1Hummelshoj LStratton PVercellini P.

 

Abstract

The association of pain and endometriosis was recognized with the first definitive published reports of this disorder. Unfortunately, the precise etiologies and pathways leading to nociception and pain symptoms in endometriosis remain poorly understood, and as a result, effective therapeutic interventions are lacking with consequent profound effects on affected women’s quality of life. In this opinion paper we summarize selected proceedings presented at the 28th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Istanbul, Turkey, and review the clinical and translational evidence of chronic pain, neurogenesis, and the pernicious impact of dyspareunia on women with symptomatic endometriosis. The effectiveness of medical treatments is critically assessed and the findings indicate that good therapeutic options are available with extant medications effective in some sub-groups of women with endometriosis, many of which are affordable globally. Nevertheless, new management strategies and drugs need to be developed to increase the options of all afflicted women to minimize and ideally eradicate painful symptoms of endometriosis. However, only by elucidating distinctions among sub-groups with specific symptoms, suggesting different mechanisms, are we likely to derive truly successful therapeutic strategies.

 

 

Aust N Z J Obstet Gynaecol. 2013 Jun;53(3):305-9.

Urinary retention following laparoscopic gynaecological surgery with or without 4% icodextrin anti-adhesion solution.

Nesbitt-Hawes EM1Zhang CSWon HRLaw KAbbott JA.

 

Abstract

BACKGROUND:

Urinary retention is a recognised complication of laparoscopic surgery. Previous work showed an association with 4% icodextrin solution and urinary retention.

AIMS:

To determine the incidence of urinary retention following laparoscopic gynaecological surgery with or without the use of 4% icodextrin.

METHODS:

A prospective observational study of 147 women undergoing laparoscopic gynaecological surgery for benign pathology. Women had their planned laparoscopic procedure and either received icodextrin solution or nothing as determined by their treating surgeon at the time of the operation.

RESULTS:

From May 2011 to February 2012, 147 women were approached to participate in the study; of whom, 124 women were included: 62 received icodextrin and 62 did not. The women in the non-icodextrin group were significantly older (P = 0.007) and had a higher BMI (P = 0.03) than those in the icodextrin group. Following surgery, 27/124 (21.8%) women had post-operative urinary retention. Icodextrin was associated with significantly more urinary retention (P = 0.017), but did not extend hospital admission significantly (P = 0.14). The administration of icodextrin was associated with resection of moderate- or severe-stage endometriosis involving multiple surgical sites, whereas women in the non-icodextrin group were more likely to be having a hysterectomy.

CONCLUSIONS:

In this non-randomised study, there were significantly more women with post-operative urinary retention when icodextrin was used; however, this did not contribute to an extended hospital admission. While there may be confounding factors, women receiving icodextrin should be warned of the possibility of urinary retention post-operatively, but that this is unlikely to affect their stay in hospital.

 

 

Evid Based Complement Alternat Med. 2013;2013:240702.

A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine.

Porpora MG1Brunelli RCosta GImperiale LKrasnowska EKLundeberg TNofroni IPiccioni MGPittaluga ETicino AParasassi T.

 

Abstract

Urged by the unmet medical needs in endometriosis treatment, often with undesirable side effects, and encouraged by N-acetylcysteine (NAC) efficacy in an animal model of endometriosis and by the virtual absence of toxicity of this natural compound, we performed an observational cohort study on ovarian endometriosis. NAC treatment or no treatment was offered to 92 consecutive Italian women referred to our university hospital with ultrasound confirmed diagnosis of ovarian endometriosis and scheduled to undergo laparoscopy 3 months later. According to patients acceptance or refusal, NAC-treated and untreated groups finally comprised 73 and 72 endometriomas, respectively. After 3 months, within NAC-treated patients cyst mean diameter was slightly reduced (-1.5 mm) versus a significant increase (+6.6 mm) in untreated patients (P = 0.001). Particularly, during NAC treatment, more cysts reduced and fewer cysts increased their size. Our results are better than those reported after hormonal treatments. Twenty-four NAC-treated patients-versus 1 within controls-cancelled scheduled laparoscopy due to cysts decrease/disappearance and/or relevant pain reduction (21 cases) or pregnancy (1 case). Eight pregnancies occurred in NAC-treated patients and 6 in untreated patients. We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy.

 

 

 

Case Rep Urol. 2013;2013:812475.

Lumbar Ureteral Stenosis due to Endometriosis: Our Experience and Review of the Literature.

Butticè S1Laganà ASBarresi VInferrera AMucciardi GDi Benedetto AD’Amico CEMagno C.

 

Abstract

Endometriosis is a chronic gynaecological disorder characterized by the presence of endometrial tissue outside the uterus. The disease most often affects the ovaries, uterine ligaments, fallopian tubes, and cervical-vaginal region. Urinary tract involvement is rare, accounting for around 1%-2% of all cases, of which 84% are in the bladder. We report a case of isolated lumbar ureteral stenosis due to endometriosis in a 37-year-old patient. The patient came to our observation complaining from lumbar back pain and presented with severe fever. The urological examination found monolateral left positive sign of Giordano. Blood tests evidenced marked lymphocytosis and increased valued of C-reactive protein. Urologic ultrasound showed hydronephrosis of first degree in the left kidney and absence of images related to stones bilaterally. Uro-CT scan evidenced ureteral stenosis at the transition between the iliac and pelvic tracts. We addressed the patient to surgery, and performed laparoscopic excision of the paraureteral bulk, endoscopic mechanical ureteral dilation, and stenting. The histological examination evidenced glandular structures lined by simple epithelium and surrounded by stroma. Immunohistochemical test of the glandular epithelium showed positivity for estrogen and progesterone receptors and moreover stromal cells were positive for CD10. The finding suggested a very rare diagnosis of isolated lumbar ureteral endometriosis.

 

 

J Indian Med Assoc. 2012 Oct;110(10):694-9.

Pregnancy outcome in pre-operative danazol treatment followed by laparoscopic correction in infertility associated with endometriosis.

Chatterjee S1Dey SChowdhury RGGanguly DD.

 

Abstract

Probably, more has been written and less has been agreed upon, regarding the pathogenesis of the enigmatic disorder–endometriosis, which is the leading cause of disability in women of reproductive age group, resulting in infertility and pelvic pain. It is an accepted fact that the medical treatment of endometriosis does not help in infertility management, except certain situations like pain, limiting the attempt of pregnancy, or endometriosispresenting with cornual block, due to endosalpingiosis. The usual treatment of infertility being either surgical correction, or assisted reproductive technology procedures. In our patient population, the acceptance of In-vitro fertilisation or embryo transfer is much less, because of its high cost and social taboo. In this series, the improved pregnancy outcome is observed with medical treatment of endometriosis with danazol before and after the laparoscopic correction of the tubo-ovarian relation due to endometriosis or in certain cases of minimal to mild endometriosis, not requiring correction. Out of 722 suspected cases of endometriosis, 576 cases were subjected to prelaparoscopic treatment with danazol, and the result was compared with 424 cases of only laparoscopic treatment, and 216 cases of postlaparoscopic danazol treatment, during the years 2004 to 2008. A total of 1216 cases were included in the study. The initiation of medical treatment in the pre-operative period gives better pregnancy outcome, as compared to only surgical or postsurgical medical treatment. The experience proves that the adjuvant medical treatment with danazol, initiated before laparoscopy in suspected endometriosis cases is useful treatment procedure, to increase the pregnancy rate.

 

 

J Altern Complement Med. 2013 Nov;19(11):853-9. doi: 10.1089/acm.2012.0623. Epub 2013 Jun 5.

Western herbal medicine, epigenetics, and endometriosis.

Stephens L1Whitehouse JPolley M.

 

Abstract

Endometriosis is an enigmatic disease characterized by the presence and growth of endometrial-like tissue outside the uterine cavity. The etiology of endometriosis is poorly understood, yet recent evidence suggests that epigenetic aberrations and heritable changes in the genome may be the key to understanding how to approach this disease. Difficulty in long-term management of endometriosis symptoms and unpredictability of treatment outcome necessitate research into other treatment modalities, such as Western herbal medicine. This article reviews commonly used herbs in the treatment of endometriosis, the effects of phytochemical constituents on endometrial cells, and the impact on the epigenome.

 

 

Hum Reprod. 2013 Aug;28(8):2026-31.

Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.

Brosens I1Gordts SBenagiano G.

 

Abstract

Endometriosis in the adolescent has, in recent years, been discovered to be a challenging problem in gynaecology. Although the pain may start at a young age, even before the onset of menstruation, the diagnosis by laparoscopy is almost always postponed for several years, by which time destructive lesions have affected the tubo-ovarian structures and severely compromised fecundability. Several factors may play a role, but one important reason for this disease progression is likely to be the delay in diagnosis. Therefore, transvaginal ultrasounds and transvaginal access with a less invasive needle endoscopy are recommended for exploration of the pelvis, diagnosis of endometriosis and treatment at an early stage before severe lesions develop.

 

 

Hum Reprod. 2013 Aug;28(8):2253-64.

BAY 1002670: a novel, highly potent and selective progesterone receptor modulator for gynaecological therapies.

Wagenfeld A1Bone WSchwede WFritsch MFischer OMMoeller C.

 

Abstract

STUDY QUESTION:

Does the novel progesterone receptor (PR) modulator BAY 1002670, based on its preclinical pharmacological profile, offer a potential novel treatment option for uterine fibroids?

SUMMARY ANSWER:

The newly synthesized BAY1002670 has proved to be a very potent, highly selective PR modulator in all in vitro and in vivo pharmacodynamics assays performed: it exhibits marked efficacy in an innovative humanized fibroid disease model, suggesting BAY 1002670 to be a very promising treatment option for uterine fibroids.

WHAT IS KNOWN ALREADY:

PR inhibiting ligands have shown clinical utility in a range of potential indications and applications. Despite the emergence of the first PR antagonist >30 years ago, no agent of this compound class has been authorized in any indication for long-term application. Among other reasons, suboptimal selectivity and safety profiles of previous candidates have led to discontinuation and modification of development programmes.

STUDY, DESIGN, SIZE, DURATION:

The preclinical studies include relevant in vitro and in vivo assays to clarify the properties of the PR modulator BAY 1002670 as well as a fibroid xenograft study to show directly the efficacy of BAY 1002670 on the human target tissue.

PARTICIPANTS/MATERIAL, SETTING, METHODS:

BAY 1002670 was tested for binding and transactivational activity towards different human steroid receptors. Activity of the compound in the corresponding in vivo models (rat, rabbit) was assessed. Furthermore, BAY 1002670 was tested in a disease model for uterine fibroids utilizing primary human tumour tissues as xenograft in immunodeficient mice treated with estradiol (E2) and progesterone (P).

MAIN RESULT AND THE ROLE OF CHANCE:

BAY1002670 in subnanomolar concentrations exhibits a highly selective binding profile and antagonistic activity for the PR. These properties are also reflected in its action in two progesterone-dependent animal models that assess the termination of pregnancy and endometrial transformation. Favourable selectivity towards other nuclear hormone receptors was demonstrated. No in vivo activity was found at the glucocorticoid, estrogenic and mineralocorticoid receptors with only weak anti-androgenic activity. In a human fibroid xenograft model BAY 1002670 showed a marked dose-dependent reduction of fibroid tumour weight gain of 95% at a dose of 3 mg/kg/day (P < 0.005).

LIMITATIONS AND REASON FOR CAUTION:

Selectivity and potency of BAY 1002670 have only been determined in vitro and in animal models so far.

WIDER IMPLICATIONS OF THE FINDING:

The PR modulator BAY 1002670 might offer a treatment option not only for uterine fibroids but also for other gynaecological indications.

STUDY FUNDING/COMPETING INTEREST:

The studies took place at Bayer Pharma AG. All authors are employees of Bayer Pharma AG. No external funding declared.

 

 

Hum Reprod. 2013 Aug;28(8):2126-33.

Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden.

Santulli P1Even MChouzenoux SMillischer AEBorghese Bde Ziegler DBatteux FChapron C.

 

Abstract

STUDY QUESTION:

Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma?

SUMMARY ANSWER:

Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight.

WHAT IS KNOWN ALREADY:

Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before.

STUDY DESIGN, SIZE, DURATION:

This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated.

MAIN RESULTS AND THE ROLE OF CHANCE:

IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5-2247.7) than in controls (median, 27.8 pg/ml; range, 7.5-71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003).

LIMITATIONS, REASONS FOR CAUTION:

There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels.

WIDER IMPLICATIONS OF THE FINDINGS:

We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis.

STUDY FUNDING/COMPETING INTEREST(S):

No funding, no conflict of interest.

 

JSLS. 2013 Jan-Mar;17(1):88-94.

A pilot feasibility multicenter study of patients after excision of endometriosis.

Yeung P Jr1Tu FBajzak KLamvu GGuzovsky OAgnelli RPeavey MWiner WAlbee RSinervo K.

 

Abstract

OBJECTIVE:

To serve as a pilot feasibility study for a randomized study of excision versus ablation in the treatment of endometriosis by (1) estimating the magnitude of change in symptoms after excision only at multiple referral centers and (2) determining the proportion of women willing to participate in a randomized trial.

METHODS:

We performed a multicenter prospective study of women undergoing excision for endometriosis(Canadian Task Force class II-3) at Duke University Center for Endometriosis Research & Treatment (currently the Saint Louis University Center for Endometriosis), Center for Endometriosis Care, Northshore University Health System, Memorial University (Canada), and Florida Hospital. The study comprised 100 female patients, aged 18 to 55 years, with endometriosis-suspected pelvic pain. The intervention was laparoscopic excision only of the abnormal peritoneum suspicious for endometriosis. The main outcome measures were quality of life, pelvic pain, dysmenorrhea, dyspareunia, and bowel and bladder symptoms.

RESULTS:

The mean follow-up period was 8.5 months. Excision of endometriosis showed a significant reduction in all pain scores except bowel symptoms, as well as significant improvement in quality of life. Of the patients, 84% were willing to participate in a randomized study.

CONCLUSIONS:

Quality of life is a needed primary outcome for any randomized study comparing excision versus ablation. A multicenter comparative trial is feasible, although quality assurance would have to be addressed. Patients were willing to be randomized even at surgical referral centers.

 

 

 

JSLS. 2013 Jan-Mar;17(1):95-9.

Robotic-assisted hysterectomy for the management of severe endometriosis: a retrospective review of short-term surgical outcomes.

Bedaiwy MA1Rahman MYChapman MFrasure HMahajan Svon Gruenigen VEHurd WZanotti K.

 

Abstract

OBJECTIVES:

The primary objective was to examine the safety and feasibility of robotic-assisted laparoscopy in a cohort of women treated surgically for stage III and IV endometriosis. The secondary objective was to explore whether the stage of endometriosis affected surgical outcome.

METHODS:

In this cohort study, 43 women with severe endometriosis were treated with robot-assisted laparoscopic hysterectomy with unilateral or bilateral salpingooophorectomy for stage III (n = 19) or stage IV (n = 24) disease.

RESULTS:

Histopathologic evaluation confirmed endometriosis in all patients, and fibroids were also shown in 12 patients. The median actual operative time was 145 min (range, 67-325 min), and the median blood loss was 100 mL (range, 20 – 400 mL). All but one of the procedures were completed successfully robotically. The length of hospital stay was 1 d for 95% of patients (41 of 43), and 2 patients had prolonged stays of 4 d and 5 d, respectively. One patient was readmitted for a vaginal cuff abscess; this represented the only complication identified in this series.

CONCLUSIONS:

Robot-assisted laparoscopic surgery appears to be a reasonably safe and feasible method for the definitive surgical management of women with severe endometriosis.

 

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