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Gynecol Obstet Invest. 2011 Sep 27. [Epub ahead of print]

Pyrrolidine Dithiocarbamate Attenuates Nuclear Factor-ĸB Activation, Cyclooxygenase-2 Expression and Prostaglandin E(2) Production in Human Endometriotic Epithelial Cells.

Zhang JJ, Xu ZM, Chang H, Zhang CM, Dai HY, Ji XQ, Li C, Wang XF.

Source

Departments of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, China.

Abstract

Background: The nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. Methods: The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA. Results: PDTC in the absence or presence of tumor necrosing factor-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis. Conclusion: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

Ginecol Obstet Mex. 2011 Aug;79(8):489-92.

Appendicular endometriosis as a cause of acute abdomen.

[Article in Spanish]

Villarreal-Peral C, Olvera-Gracida L, González-Maynes Mde L, Saucedo-Ruiz G.

Source

Hospital General Rincón de Romos, Aguascalientes, México.

Abstract

Endometriosis affects between 4 and 17% of women of reproductive age. The intestinal endometriosis affects 3 to 12% of women and is usually asymptomatic when it affects the subserosa or serosa; 0.7 to 2.5% of patients require surgical treatment for symptomatic lesions with diarrhea, constipation, pain and hematochezia. We report a case of a patient with appendiceal endometriosis in which the diagnosis was made during an emergency surgery and histopathology reported

Ginecol Obstet Mex. 2011 Jul;79(7):441-6.

Transmural rectal endometriosis as a cause of chronic constipation. A case report and literature review.

[Article in Spanish]

Hernández Magro PM, Barrón Vega R, Rivas Larrauri E, Godínez Guerrero MA, Pérez González M, López Patiño S.

Source

Departamento de Cirurgía de colon y recto, Hospital Guadalupano de Celaya y Médica Avanzada de Celaya, Guanajunato, México. paulinomhm@hotmail.com

Abstract

The incidence of intestinal endometriosis is reported between 5.3 and 12% of cases and of these, between 70 and 93% are located in the rectum and sigmoid. We report the case of a 32-year-old with constipation and bloating and cramping pain during the last 2 years. The pain increased in frequency during the past 6 months. From the data obtained from physical examination and imaging studies may be suspected pelvic endometriosis with infiltration of anterior rectal wall. Resection of the low anterior rectum with colo-rectal anastomosis was performed, with adequate surgical outcome and resolution of symptoms. In patients of childbearing age with abdominal or pelvic pain, constipation of recent onset or occlusive bowel, which may or may not be related to the menstrual cycle should be considered transmural infiltration by endometrial tissue.

Urology. 2011 Sep 28. [Epub ahead of print]

Prevalence and Management of Urinary Tract Endometriosis: A Clinical Case Series.

Gabriel B, Nassif J, Trompoukis P, Barata S, Wattiez A.

Source

Department of Gynecologic Surgery, Strasbourg University Hospital Hautepierre and CMCO, and IRCAD/EITS, Strasbourg, France; Universitäts-Frauenklinik Freiburg, Freiburg, Germany.

Abstract

OBJECTIVE:

To report on the prevalence, surgical management, and outcome of urinary tract endometriosis (UTE) in a cohort of 221 patients undergoing laparoscopic surgery for severe endometriosis. UTE can cause significant morbidity, such as silent kidney or progressive renal function loss. Its frequency is underestimated and data on laparoscopic management are scarce.

METHODS:

Between 2007 and 2010, 43 patients were eligible for this single-center, retrospective study. The inclusion criterion was the presence of UTE (ie, bladder and/or ureteral endometriosis). All patients were operated laparoscopically.

RESULTS:

The prevalence of UTE was 19.5% (43/221). There was no correlation between bladder and ureteral endometriosis (P >.05). Ureteral endometriosis was associated with patient’s age (P <.01). Patients with bladder, but not ureteral, involvement complained more frequently about dysuria, hematuria, and urinary tract infections. Intraoperative and magnetic resonance imaging (MRI) findings revealed a moderate to good correlation. UTE was not associated with rectovaginal or bowel endometriosis, but rather with involvement of the uterosacral ligaments (P <.01). Twenty-two patients with bladder endometriosis were treated by mucosal skinning and 11 patients underwent partial cystectomy. Superficial ureteral excision was performed in 4 patients, whereas resection with ureteroureterostomy was done in 9 patients. There was no difference regarding the intra- and postoperative complications in patients with or without UTE.

CONCLUSION:

In severe pelvic endometriosis, involvement of the urinary tract is quite common. Laparoscopic management is feasible and safe. Because of the lack of specific symptoms, the preoperative diagnosis of ureteral endometriosis still remains a challenge. Pelvic MRI represents a useful preoperative diagnostic tool.

Fertil Steril. 2011 Oct;96(4):939-42. Epub 2011 Aug 24.

Aromatase inhibition for refractory endometriosis-related chronic pelvic pain.

Abushahin F, Goldman KN, Barbieri E, Milad M, Rademaker A, Bulun SE.

Source

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois; Florida Gynecologic Oncology, Fort Myers, Florida.

Abstract

OBJECTIVE:

To evaluate the use of an aromatase inhibitor for the treatment of endometriosis-related chronic pelvic pain.

DESIGN:

Retrospective analysis.

SETTING:

Academic medical center outpatient reproductive endocrinology clinic.

PATIENT(S):

Sixteen patients with endometriosis and chronic pelvic pain who previously failed conventional medical and/or surgical therapy.

INTERVENTION(S):

Treatment with the aromatase inhibitor letrozole (2.5 mg/d) plus a gonadotropin suppressor (norethindrone acetate, 2.5 mg/d, or a combination oral contraceptive [OC]) for an average of 6 months.

MAIN OUTCOME MEASURE(S):

Pain scores were reported at each visit using a visual analogue scale from 0 to 10 (0: no pain, 10: maximum pain).

RESULT(S):

Sixteen patients were treated with an aromatase inhibitor for 180 ± 31days. The median pain score at the start of therapy was 7, and at the end of therapy it was 1.5. In the nine patients who were evaluated after discontinuing therapy, pain scores returned to pretreatment levels. We did not find any correlation between the length of treatment and the overall improvement in pain score.

CONCLUSION(S):

Letrozole plus a gonadotropin suppressor substantially improved pain symptoms in patients with endometriosis refractory to conventional therapies; however, pain recurred after treatment was completed.

Fertil Steril. 2011 Oct;96(4):880-3. Epub 2011 Aug 15.

Elevated serum alpha-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization.

Jungheim ES, Macones GA, Odem RR, Patterson BW, Moley KH.

Source

Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri.

Abstract

OBJECTIVE:

To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy.

DESIGN:

Prospective cohort.

SETTING:

University hospital.

PATIENT(S):

Ninety-one women undergoing IVF.

INTERVENTION(S):

Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids.

MAIN OUTCOME MEASURE(S):

Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy.

RESULT(S):

In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686).

CONCLUSION(S):

Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both.

Fertil Steril. 2011 Oct;96(4):943-950.e1. Epub 2011 Aug 6.

Adenomyosis does not affect implantation, but is associated with miscarriage in patients undergoing oocyte donation.

Martínez-Conejero JA, Morgan M, Montesinos M, Fortuño S, Meseguer M, Simón C, Horcajadas JA, Pellicer A.

Source

Instituto Valenciano de Infertilidad, Valencia, Spain.

Abstract

OBJECTIVE:

To evaluate the effect of adenomyosis on endometrial gene expression and its correlation with clinical outcome.

DESIGN:

Transcriptomic analysis of the endometrium of women with adenomyosis during the window of implantation. Retrospective matched cohort study of the impact of adenomyosis on oocyte donation (OD) outcome.

SETTING:

University-affiliated infertility clinic (2005-2009).

PATIENT(S):

Endometrial samples were analyzed using microarrays in women with adenomyosis and healthy controls. The clinical study included three groups: adenomyosis, endometriosis, and control.

INTERVENTION(S):

Endometrial biopsies in natural cycles 7 days after the LH peak; controlled ovarian stimulation in donors; ET in recipients after replacement therapy.

MAIN OUTCOME MEASURE(S):

Differentially expressed genes; implantation, pregnancy, miscarriage, and term pregnancy rates in OD.

RESULT(S):

There is a similar endometrial gene expression pattern in both the adenomyosis group and controls, and nonparametric tests revealed 34 dysregulated genes in adenomyosis patients but none belonged to the group of window of implantation genes. Implantation in OD did not differ among the three groups. However, miscarriage was significantly higher in the adenomyosis group vs. the adenomyosis + endometriosis and control groups. Term pregnancy rate was also significantly lower in the adenomyosis group compared with others.

CONCLUSION(S):

Clinical and molecular data show that implantation is not affected by adenomyosis, but the higher miscarriage rates associated with this condition lead to lower term pregnancy rates, indicating a clear negative effect on the final outcome of OD.

Fertil Steril. 2011 Oct;96(4):1021-1028.e1. Epub 2011 Aug 6.

Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo.

Xu H, Becker CM, Lui WT, Chu CY, Davis TN, Kung AL, Birsner AE, D’Amato RJ, Wai Man GC, Wang CC.

Source

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

Abstract

OBJECTIVE:

To investigate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo.

DESIGN:

Animal studies.

SETTING:

University laboratory.

ANIMAL(S):

Human endometrium from women with endometriosis (n = 10) was transplanted into immunocompromised mice.

INTERVENTION(S):

Mice (n = 30) were randomly treated with EGCG, vitamin E (antioxidant control), or vehicle (negative control) for microvessel imaging.

MAIN OUTCOME MEASURE(S):

Endometriotic implants were collected for angiogenesis microarray and pathway analysis. Differentially expressed angiogenesis molecules were confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Effects of EGCG on angiogenesis signal transduction were further characterized in a human endothelial cell line. Microvessel parameters and the angiogenesis signaling pathway in endometriotic implants and endothelial cells were studied.

RESULT(S):

EGCG, but not vitamin E, inhibited microvessels in endometriotic implants. EGCG selectively suppressed vascular endothelial growth factor C (VEGFC) and tyrosine kinase receptor VEGF receptor 2 (VEGFR2) expression. EGCG down-regulated VEGFC/VEGFR2 signaling through c-JUN, interferon-γ, matrix metalloproteinase 9, and chemokine (C-X-C motif) ligand 3 pathways for endothelial proliferation, inflammatory response, and mobility. EGCG also suppressed VEGFC expression and reduced VEGFR2 and ERK activation in endothelial cells. VEGFC supplementation attenuated the inhibitory effects by EGCG.

CONCLUSION(S):

EGCG inhibited angiogenesis and suppressed VEGFC/VEGFR2 expression and signaling pathway in experimental endometriosis in vivo and endothelial cells in vitro.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):260-4. Epub 2011 Jul 20.

Combination of polymorphisms in luteinizing hormone β, estrogen receptor β and progesterone receptor and susceptibility to infertility and endometriosis.

Christofolini DM, Vilarino FL, Mafra FA, André GM, Bianco B, Barbosa CP.

Source

Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, SP, Brazil.

Abstract

OBJECTIVES:

To determine whether the combination of PR (PROGINS), ERβ G+1730A and/or LHβ G1502A polymorphisms in infertile women with and without endometriosis and in a control group increases the risk of infertility and/or endometriosis.

STUDY DESIGN:

Case-control study including 201 infertile women with endometriosis, 80 infertile women without endometriosis and 206 fertile women as control group. PROGINS was identified by PCR (polymerase chain reaction) and ERβ G+1730A and LHβ G1502A were identified by PCR-RFLP (restriction fragment length polymorphism).

RESULTS:

A statistically significant difference was found for the combination of LHβ+ERβ polymorphisms among infertile patients with endometriosis and control group (p=0.003, OR=2.468), among infertile patients with endometriosis I/II and control group (p=0.002, OR=3.081), among infertile patients with endometriosis III/IV and control group (p=0.035, OR=2.136) and for the combination of LHβ+PROGINS polymorphisms among infertile patients with endometriosis I/II and control group (p=0.014, OR=3.081). However, the odds of developing endometriosis are not enhanced in the presence of the two polymorphisms, being similar to the odds when only LH polymorphism is present.

CONCLUSIONS:

Individually, the presence of LHβ G1502A and ERβ G+1730A polymorphisms is associated with infertility and endometriosis associated infertility. However, when two polymorphisms are present in the same individual it does not appear to increase the chance of developing endometriosis or infertility.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):314-8. Epub 2011 Jun 22.

Nutrient intake, anthropometric data and correlations with the systemic antioxidant capacity of women with pelvic endometriosis.

Savaris AL, do Amaral VF.

Source

Pontifícia Universidade do Paraná, Curitiba, Brazil.

Abstract

OBJECTIVE:

Endometriosis is a multifactorial disease of uncertain etiology. There is currently insufficient evidence to assess the participation of nutritional and anthropometric aspects and their association with systemic oxidative stress.

STUDY DESIGN:

Twenty-five women with endometriosis and twenty controls were selected and evaluated to determine calorie and nutrient intake, to obtain data on body composition and analyze antioxidant capacity by measuring total serum thiol levels using DTNB (5,5′-dithiobis-(2-nitrobenzoic acid).

RESULTS:

Mean total daily calorie intake in the women in the endometriosis group was significantly higher than that of the women in the control group (p=0.005). With respect to nutrient intake, the only statistically significant difference found referred to a higher intake of fiber in the endometriosis group and of polyunsaturated fatty acids in the control group (p<0.05).

CONCLUSIONS:

Nutrient intake by the women in the endometriosis group was similar to that of women in the control group, the only differences being a higher intake of fiber in the endometriosis group and of polyunsaturated fatty acids in the control group. Antioxidant capacity was lower in the women with endometriosis but there was no correlation with nutrient intake or overweight.

J Gynecol Obstet Biol Reprod (Paris). 2011 Oct;40(6):572-6. Epub 2011 Jun 17.

Umbilical endometriosis in women free of abdominal surgical antecedents.

[Article in French]

Abramowicz S, Pura I, Vassilieff M, Auber M, Ness J, Denis MH, Marpeau L, Roman H.

Source

Clinique gynécologique et obstétricale, CHU Charles-Nicolle, 1, rue de Germont, 76031 Rouen, France.

Abstract

Primary umbilical endometriosis represents a very rare localization of the disease and is represented by blue, papular, nodular or cystic lesions whose symptoms are related to ovarian cycle. We report the management of three women, free of surgical antecedents presenting with primary umbilical endometriosis. In each woman, abdominal laparoscopy revealed peritoneal pelvic endometriosis. The excision of umbilical lesions was performed with satisfactory esthetical outcomes. In our experience, umbilical endometriosis responsible for highly characteristic features appears playing the role of clinical marker for pelvic endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):285-8. Epub 2011 Jun 12.

Predisposition of subtle endometriotic lesions predominantly on the left side assessed by transvaginal hydrolaparoscopy (THL).

Kissler S, Marx K, Scholtes M, Pfeiffer S, Meier W, Neulen J.

Source

Interdisciplinary IVF-Centre Duesseldorf, Germany.

Abstract

OBJECTIVE:

Endometriosis is one of the most frequent gynaecological disorders being associated with infertility. Hence, the early detection of endometriosis in infertility patients is of importance for the treatment modalities in infertility. Transvaginal hydrolaparoscopy (THL) offers an accurate, safe and quick diagnostic tool, not only for the evaluation of the fallopian tubes but also for the detection of very subtle endometriotic lesions in the early stages of endometriosis.

STUDY DESIGN:

Between January 2008 and January 2010, we conducted a study in order to evaluate the prevalence, extent and localisation of endometriosis via the new technique of THL in infertility patients. 239 patients with a mean age of 33.9 years underwent THL after having given informed consent.

RESULTS:

In 237 patients, access to the cul-de-sac was successfully achieved. Endometriosis was detected in 77 of 237 cases (32.5%). In 85.7% of cases, the endometriotic lesions were classified as very small (ASRM stage I°). Predominantly, the small lesions were found merely on the left side of the patient’s peritoneal cavity: in 43 cases (55.8%), endometriosis was detected strictly on the left side, whereas the disease was detected on the right side in only 5 patients (6.5%). In 29 patients, endometriosis could be detected in both sides of the pelvis (37.7%). The differences in the side-dependent distribution were statistically highly significant (p<0.0001). In most of the cases, the subtle endometriotic lesions affected the ovarian surface superficially (53.5%) or the peritoneum of the lateral pelvic wall (25.6%).

CONCLUSIONS:

These data clearly indicate that there is a high prevalence of endometriosis in patients with infertility. THL is an accurate, safe and quick method for a thorough examination of the female pelvis besides the patency of the fallopian tubes. The high prevalence of left-sided subtle endometriotic lesions must be interpreted that during THL a very early process in the development of endometriosis can be observed. Even minimal to mild endometriosis might lead to a significant restriction in uterotubal transport capacity whose integrity is directly correlated to normal pregnancy rates. The extent of the accompanying adenomyosis is directly correlated to the loss of intact uterotubal transport capacity.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):298-304.

Effect of the bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of endometrial implants in Wistar rats.

Kondo W, Dal Lago EA, Francisco JC, Simeoni RB, de Noronha L, Martins AP, de Azevedo ML, Ferreira CC, Maestrelli P, Olandoski M, Guarita-Souza LC, do Amaral VF.

Source

Department Center for Health and Biological Sciences, Pontifical Catholic University of Parana (PUC-PR), Brazil.

Abstract

OBJECTIVE:

To study the effect of bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of surgically induced endometriosis in an experimental model.

STUDY DESIGN:

This is an experimental study conducted in the Center for Health and Biological Sciences at the Pontifical Catholic University of Parana, Brazil. Endometriotic implants were surgically induced in 120 female Wistar rats. The animals with viable endometrial implant (larger than 25mm(2)) were randomically divided into 3 groups to receive an intraperitoneal injection of 0.2cc of saline solution (C group; n=30), a subcutaneous injection of 1mg/kg of leuprolide (L group; n=34), or an intraperitoneal injection of 5×10(6) bone marrow derived-mononuclear stem cells (SC group; n=36). They were sacrificed after 21 days to assess the implants’ size and the tissue expression of vascular endothelial growth factor receptor (VEGF-R) and tumor necrosis factor-alpha (TNF-alpha).

RESULTS:

Treatment with leuprolide decreased the surface area of the endometriotic implant compared to the SC group and the C group. The absolute reduction in the surface area of the implant was 16.5mm, 0mm, and 0mm (p=0.007), respectively, and the percent reduction was 40.2%, 0%, and 0% (p=0.001). VEGF-R expression in the endometriotic implant decreased after treatment in the L and SC groups compared to the C group (409.6μm(2) vs. 465μm(2) vs. 920.9μm(2), respectively; p=0.021). TNF-alpha expression also reduced in the L and SC groups compared to the C group (585.7μm(2) vs. 549.3μm(2) vs. 2402.1μm(2), respectively; p<0.001).

CONCLUSION:

Bone marrow derived-mononuclear stem cells transplantation decreased the expression of VEGF-R and TNF-alpha in the endometriotic implant but did not reduce the surface area of the lesion.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):289-93. Epub 2011 May 31.

The impact of deep disease on surgical treatment of endometriosis.

Setälä M, Kössi J, Silventoinen S, Mäkinen J.

Source

Department of Obstetrics and Gynecology, Päijät-Häme Central Hospital, Lahti, Finland.

Abstract

OBJECTIVE:

To compare the difficulty of surgery in patients with and without deeply infiltrating endometriosis.

STUDY DESIGN:

Prospective cohort study performed in one hospital specialized in the surgical treatment of endometriosis. 193 consecutive patients undergoing excision of all visible endometriosis by laparoscopy (176 patients, 91.2%) or by laparotomy (17 patients, 8.2%). The duration of surgery, the number of operations, the number of day-surgery operations, the need to operate with a surgeon, the ability to perform complete excision during one operation, and the ability to perform operation by laparoscopy were compared in patients with and without deep lesions.

RESULTS:

The mean duration of surgery was 192 (SD 96), and 76 (SD 41)min in patients with and without deep lesions (p<0.001). Ureterolysis (66% vs. 20%, p<0.001), division of adhesions (92% vs. 69%, p<0.001), and hysterectomy (32% vs., 8%, p<0.001), were more often performed on patients with deep lesions. 41 patients (42%) with deep lesions, and 1 patient (1%) without deep lesions were operated with a surgeon (p<0.001). Day-surgery was less often performed on patients with deep lesions (11% vs. 45%, p<0.001). Complete excision during one operation was performed on 95% and on 97% of the patients with and without deep lesions (p=1.0). Complete excision was less often performed by laparoscopy in patients with deep lesions (79% vs. 95%, p<0.001).

CONCLUSIONS:

Surgical treatment of deep lesions is more demanding and time-consuming than surgical treatment of other types of endometriosis, and collaboration with a surgeon is often necessary. Complete excision during one operation is a realistic goal for endometriosis surgery, but it is significantly less often achievable by laparoscopy in patients with deep lesions than in patients without deep lesions.

Eur J Obstet Gynecol Reprod Biol. 2011 Oct;158(2):265-8. Epub 2011 May 26.

Laparoendoscopic single-site surgery (LESS) for adnexal tumors: one surgeon’s initial experience over a one-year period.

Kim WC, Lee JE, Kwon YS, Koo YJ, Lee IH, Lim KT.

Source

Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, Republic of Korea.

Abstract

OBJECTIVE:

In this article, we present our initial experience with laparoendoscopic single-site surgery (LESS) for adnexal tumors and report on the safety and feasibility of this technique.

STUDY DESIGN:

We retrospectively reviewed the medical records of the first 94 consecutive patients who underwent LESS for adnexal tumors at Cheil General Hospital and Women’s Healthcare Center, Seoul, Korea between March 2009 and July 2010. Our retrospective chart review was approved by our local Institutional Review Board (IRB). We used a homemade wound retractor and surgical glove as the single-port device. All LESS procedures were performed by a single surgeon.

RESULTS:

Of 94 patients, 90 (95.7%) successfully underwent LESS for the treatment of an adnexal tumor. The mean age of the patients was 38.51±11.65 years, and the mean body mass index was 21.22±2.79kg/m(2). The mean operative time was 50.33±13.26min, and the mean diameter of the adnexal tumors was 6.26±3.19cm. The procedures included enucleation of an ovarian cyst (n=56), salpingo-oophorectomy (n=32), and salpingectomy (n=4). Two cases with suspicion for malignancy underwent conversion to laparotomy (2.1%), and frozen sections revealed serous ovarian adenocarcinoma (n=1) and chronic inflammation (n=1). Except for those two cases, the pathologic diagnoses were confirmed as mature cystic teratoma (n=30), endometriosis (n=24), mucinous cystadenoma (n=14), serous cystadenoma (n=14), borderline ovarian tumor (n=4), hydrosalpinx (n=4), serous adenocarcinoma of the salpinx (n=1), and ectopic pregnancy (n=1). Two cases required an additional trocar for adhesiolysis of severe pelvic adhesion. No major intraoperative or postoperative complications occurred.

CONCLUSIONS:

Our results suggest that LESS is a safe and feasible alternative to conventional laparoscopic surgery for the treatment of adnexal tumors.

Reprod Sci. 2011 Oct;18(10):941-7.

Remission of endometriosis by hyperbaric oxygen treatment in rats.

Aydin Y, Atis A, Uludag S, Tezer I, Sakiz D, Acar H, Toklu A.

Source

1Department of Obstetrics and Gynecology of Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Abstract

We designed this prospective, randomized controlled animal study to determine the effects of hyperbaric oxygen (HBO) on experimentally induced endometriosis in a rat model. Surgical induction of endometriosis was performed in 40, nonpregnant, female, Wistar-Albino rats at the Experimental Medicine Research Center of Istanbul University (DETAE). Four weeks later, the first and second laparotomies for volume measurement and peritoneal fluid (PF) collection were performed, and the rats were divided randomly into the study and control groups. The study group was exposed to HBO treatment for 6 weeks. Then, a third laparotomy was performed on all of the rats. The volume, histopathologic scores, Ki-67 labeling of the endometriotic implants, and the levels of tumor necrosis factor-α (TNF-α) in the PF were measured. The mean volume of the endometriotic implants in the study group was significantly lower than that of the control group at the end of the study (57.4 ± 12.5 vs 94.6 ± 17.2 mm(3)). The mean histopathological scores (1.60 ± 0.50 vs 2.42 ± 0.51), Ki-67 immunohistochemical scores (1.50 ± 0.51 vs 2.37 ± 0.49) of the endometriotic implants, and the TNF-α levels (5.33 ± 1.02 vs 8.16 ± 1.76 pg/mL) were significantly lower in the study group than in the control group. Hyperbaric oxygen treatment for 2 hours a day for 6 weeks resulted in significant remission of endometriosis in rats.

Fertil Steril. 2011 Sep 27. [Epub ahead of print]

Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes.

Trabert B, Schwartz SM, Peters U, De Roos AJ, Chen C, Scholes D, Holt VL.

Source

University of Washington, Seattle, Washington; Fred Hutchinson Cancer Research Center, Seattle, Washington.

Abstract

OBJECTIVE:

To evaluate the relationship between common genetic variation in genes involved in the biosynthesis and signaling of estrogen and progesterone and endometriosis risk.

DESIGN:

Genetic polymorphism analysis.

SETTING:

Population-based case-control study conducted in Group Health Cooperative enrollees in western Washington.

PATIENT(S):

Women with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001 (n = 256) and age- and reference year-matched female control subjects without a history of endometriosis (n = 567).

INTERVENTIONS(S):

None.

MAIN OUTCOME MEASURE(S):

We evaluated the relationship between common genetic variation and endometriosis risk, using gene-based tests and single-variant analysis of genetic polymorphisms in ESR1, ESR2, PGR, CYP17A1, CYP19A1, HSD17B1, HSD17B2, CYP1A1, CYP1A2, COMT, and GSTM1.

RESULT(S):

The most consistent gene-based association with endometriosis risk was for CYP19A1. We did not find evidence for consistent significant associations between previously reported candidate SNPs in sex hormone-related genes and endometriosis risk.

CONCLUSION(S):

In summary, we report increased endometriosis risk with CYP19A1 gene-based tests; replication of the association between endometriosis and this gene or gene region is necessary in a larger study population.

J Reprod Immunol. 2011 Sep 27. [Epub ahead of print]

Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis.

Michaud N, Al-Akoum M, Gagnon G, Girard K, Blanchet P, Rousseau JA, Akoum A.

Source

Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec, Québec, Canada.

Abstract

Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic inflammation, and natural specific inhibitors, including soluble IL1 receptor accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are critical for counterbalancing the pleiotropic effects of IL1. The objective of this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2 and IL1β, in the peritoneal fluid of women with and without endometriosis. Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA. sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV. sIL1R2 concentrations were decreased, and those of IL1β were significantly increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were significantly decreased in the secretory phase of the menstrual cycle, and IL1β concentrations were elevated in the proliferative and the secretory phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with endometriosis who were infertile, fertile, suffering from pelvic pain or pain-free. However, IL1β concentrations were significantly reduced in women with endometriosis who were infertile or had pelvic pain. These changes may exacerbate the local peritoneal inflammatory reaction observed in women with endometriosis and contribute to endometriosis pathophysiology and the major symptoms of this disease.

J Clin Endocrinol Metab. 2011 Sep 28. [Epub ahead of print]

MicroRNA 135 Regulates HOXA10 Expression in Endometriosis.

Petracco R, Grechukhina O, Popkhadze S, Massasa E, Zhou Y, Taylor HS.

Source

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Ahaven, Connecticut 06520.

Abstract

Context:Homeo box A10 (HOXA10) regulates endometrial receptivity and its expression is decreased in women with endometriosis. Although sex steroids regulate HOXA10, these hormones are unaltered in endometriosis. We hypothesized a role for microRNA in the regulation of HOXA10.Objective:MicroRNA 135a and -b are small noncoding RNA with predicted targets that include HOXA10. We evaluated miR135a/b expression and HOXA10 regulation in endometrium from subjects with and without endometriosis.Design:The design of the study was the measurement of miR135a/b expression by quantitative PCR and in vitro analysis of HOXA10 regulation.Setting:The study was conducted at a university medical center.Patients:Patients included 50 controls and 32 women with endometriosis.Interventions:Study interventions included endometrial biopsies and in vitro transfection.Main Outcome Measures:miR135a/b and HOXA10 expression were measured in the study.Results:All endometrial samples expressed miR135a and -b. miR135a expression in controls was increased during the proliferative phase, decreased at the time of ovulation, and increased during the luteal phase. Subjects with endometriosis had 3-fold higher expression of miR135a in the proliferative phase than controls. miR135b showed less variation across the menstrual cycle; however, it was significantly increased in women with endometriosis in the proliferative and secretory phases. HOXA10 expression was simultaneously repressed in the endometrium of women with endometriosis. Transfection of endometrial stromal cells with mir135a/b or miR135a/b inhibitors resulted in the altered expression of HOXA10 mRNA and protein. miR135a or -b decreased luciferase expression driven by the HOXA10 3′ untranslated region containing the miR135 binding site. miR135a regulation of HOXA10 was absent in MCF-7 cells, demonstrating cell specificity.Conclusions:HOXA10 was aberrantly regulated in the endometrium of women with endometriosis by both miR135a and miR135b. Increased microRNA expression likely suppresses genes required for implantation.

Pharm Stat. 2011 Sep;10(5):410-3. doi: 10.1002/pst.507. Epub 2011 Sep 19.

Determining the non-inferiority margin for patient reported outcomes.

Gerlinger C, Schmelter T.

Source

Bayer Pharma AG – Global Clinical Statistics. christoph.gerlinger@bayer.com.

Abstract

One of the cornerstones of any non-inferiority trial is the choice of the non-inferiority margin delta. This threshold of clinical relevance is very difficult to determine, and in practice, delta is often “negotiated” between the sponsor of the trial and the regulatory agencies. However, for patient reported, or more precisely patient observed outcomes, the patients’ minimal clinically important difference (MCID) can be determined empirically by relating the treatment effect, for example, a change on a 100-mm visual analogue scale, to the patient’s satisfaction with the change. This MCID can then be used to define delta. We used an anchor-based approach with non-parametric discriminant analysis and ROC analysis and a distribution-based approach with Norman’s half standard deviation rule to determine delta in three examples endometriosis-related pelvic pain measured on a 100-mm visual analogue scale, facial acne measured by lesion counts, and hot flush counts. For each of these examples, all three methods yielded quite similar results. In two of the cases, the empirically derived MCIDs were smaller or similar of deltas used before in non-inferiority trials, and in the third case, the empirically derived MCID was used to derive a responder definition that was accepted by the FDA. In conclusion, for patient-observed endpoints, the delta can be derived empirically. In our view, this is a better approach than that of asking the clinician for a “nice round number” for delta, such as 10, 50%, π, e, or i. Copyright © 2011 John Wiley & Sons, Ltd.

 

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