J Pak Med Assoc. 2009 Jan;59(1):30-4.
Frequency of endometriosis among infertile women and association of clinical signs and symptoms with the laparoscopic staging of endometriosis.
Department of Biological and Biomedical Sciences, Aga Khan University Hospital, Karachi, Pakistan.
OBJECTIVE: The study aimed to determine the frequency of endometriosis in women who underwent diagnostic laparoscopy for evaluation of infertility and the association of clinical, ultrasonographic and laparoscopic findings of endometriosis with the laparoscopic stages of the disease. METHOD: It was a retrospective study of women presenting to gynaecologic clinics of the Aga Khan University Hospital from January 1999 to December 2005 with primary complaint of primary or secondary infertility and were diagnosed with endometriosis through laparoscopy. Relevant demographic and clinical information was entered and analyzed in SPSS version 14.0. RESULTS: The frequency of endometriosis in women with primary compliant of infertility was found to be 16.8%. Statistically significant associations was found between staging of the disease and thin built (p=0.007) and restricted uterine mobility on pelvic examination (p=0.035). The patients’ ultrasound and laparoscopic examination showed significant association with staging of the disease with the presence of cysts on ultrasound (p-value < 0.0001) and adhesions on laparoscopy (p value <0.00001). CONCLUSION: The variability of the definition and inconsistency in diagnostic methods makes the prevalence of endometriosis difficult to determine and we might underestimate the true burden of the disease. Most of the signs and symptoms of endometriosis do not correlate with the severity (staging) of the disease. Hence, Laparoscopy remains the gold standard for diagnosis as well as staging of endometriosis.
Reprod Sci. 2009 Feb;16(2):216-29.
Inflammation in reproductive disorders.
Department of Obstetric and Gynecology, New Jersey Medical School, Newark, New Jersey, USA.
Inflammatory disorders account for a significant percentage of gynecologic disease, particularly in reproductive age women. Inflammation is a basic method by which we respond to infection, irritation, or injury. Inflammation is now recognized as a type of nonspecific immune response, either acute or chronic. In gynecology, inflammation leads to anatomic disorders primarily as a result of infectious disease; however inflammation can affect ovulation and hormone production as well as be associated with endometriosis. Similarly, immune cell trafficking is an important component of cyclic endometrial development in each menstrual cycle. These immune cells are required for endometrial function, producing a vast array of inflammatory cytokines. Inflammation alters endometrial receptivity, however it may also play a role in tissue repair and remodeling. Finally, inflammation affects the trophoblast and trophoblast-endometrial interaction. Some components of the immune response are required for optimal fertility and normal tissue remodeling. A better understanding of the necessary role of inflammation in reproduction will allow more rational and targeted treatment of inflammatory disorders in reproductive medicine.
Reprod Sci. 2009 Feb;16(2):152-61.
Nonhuman primate models for translational research in endometriosis.
Department of Obstetrics and Gynaecology, Leuven, University Fertility Center, University Hospital Gasthuisberg, Leuven, Belgium. email@example.com
Endometriosis, defined as the ectopic presence of endometrial-like cells, is associated with infertility and pelvic pain in women. Whereas pathogenesis and spontaneous evolution of endometriosis are still poorly understood, recurrences after surgical therapy or after medical treatment are common. Spontaneous endometriosis occurs only in women and in nonhuman primates (NHPs). Inbred rhesus monkeys kept in colonies offer an attractive preclinical model to study the inheritance of spontaneous endometriosis. Baboons with spontaneous or induced endometriosis appear to be the best NHP model to study pathogenesis, pathophysiology, spontaneous evolution and new medical treatment options. In baboons, induction of endometriosis after intrapelvic injection of menstrual endometrium leads to biological changes in peritoneal cavity and in endometrium. This induction process may allows the study of cause-effect relationships which may lead to the discovery of new biomarkers for the development of new non-invasive diagnostic tests and drugs that may prevent or treat endometriosis.
Reprod Sci. 2009 Feb;16(2):126-39.
Stem cells and female reproduction.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, Connecticut 06520, USA.
Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent.
Ugeskr Laeger. 2009 Feb 2;171(6):437.
[Article in Danish]
Kollelevbakken 16, DK-2830 Virum. firstname.lastname@example.org
Inguinal endometriosis is a rare manifestation of endometriosis. Four cases are presented. In three of these cases proper diagnosis was delayed due to differential diagnostic difficulties as the symptoms in these cases were interpreted as hernia. In two cases the patient underwent hernia surgery. In inguinal lump cases in fertile women, endometriosis should be considered if accompanied by dysmenorrhoea or deep dyspareunia. In such cases MRI (magnetic resonance imaging) scans often yield further diagnostic information. If surgery is needed, it should be performed in a gynaecological setting to facilitate full surgical intervention including abdominal laparoscopy and excision.
Hum Reprod. 2009 May;24(5):1018-24. Epub 2009 Feb 6.
Combination of transvaginal sonography and clinical examination for preoperative diagnosis of pelvic endometriosis.
Department of Obstetrics and Gynaecology, Centre for Endometriosis, Villach General Hospital, Nikolaigasse 43, 9500 Villach, Austria. email@example.com
BACKGROUND: The aim of the present study was to evaluate the accuracy of routine clinical examination (per vaginam, PV) combined with transvaginal sonography (TVS) for presurgical, non-invasive diagnosis of endometriosis. METHODS: Two-hundred women with symptoms suggestive of endometriosis were prospectively assessed by PV and TVS prior to laparoscopy and radical resection of disease and histological confirmation. RESULTS: Prevalence of endometriosis on the right/left (r/l) ovary, r/l uterosacral ligament (USL), pouch of Douglas (POD), vagina, bladder, rectovaginal space (RVS) and rectum was 12%, 13%, 12%, 22%, 15%, 11%, 2%, 4% and 24%. Sensitivities, specificities, positive and negative predictive values and positive and negative likelihood ratios for combined use of TVS and PV resulted in 96/100%, 100/99%, 100/93%, 93/100% and -;0.04/87.0;- for the r/l ovarian endometriosis; 67/84%, 97/86%, 73/62%, 96/95% and 19.56;0.35/5.97;0.19 for the r/l USL disease; 87%, 98%, 90%, 98% and 49.11;0.14 for involvement of the POD; 82%, 99%, 95%, 98% and 145.64;0.18 for vaginal endometriosis; 88%, 99%, 78%, 99% and 84.0;0.13 for endometriosis of the RVS; 75%, 98%, 50%, 99% and 49.0;0.25 for bladder involvement and 96%, 98%, 94%, 99% and 48.56;0.04 for rectal endometriosis. CONCLUSIONS: The combination of PV and TVS accurately predicts the presence of endometriosis affecting the ovaries, vagina, rectum, USL, RVS and POD in patients with suspected endometriosis. We suggest the routine combination of PV and TVS as an essential part of the standard primary assessment of pelvic pain patients with suspected endometriosis.
Fertil Steril. 2009 Feb 5. [Epub ahead of print]
Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis.
Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil; Department of Gynecology and Obstetrics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
OBJECTIVE: To elucidate the potential mechanisms involved in the physiopathology of endometriosis. We analyzed the differential gene expression profiles of eutopic and ectopic tissues from women with endometriosis. DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENT(S): Seventeen patients in whom endometriosis was diagnosed and 11 healthy fertile women. INTERVENTION(S): Endometrial biopsy specimens from the endometrium of healthy women without endometriosis and from the eutopic and ectopic endometrium tissues of patients with endometriosis were obtained in the early proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Six paired samples of eutopic and ectopic tissue were analyzed by subtractive hybridization. To evaluate the expression of genes found by rapid subtraction hybridization methods, we measured CTGF, SPARC, MYC, MMP, and IGFBP1 genes by real-time polymerase chain reaction in all samples. RESULT(S): This study identified 291 deregulated genes in the endometriotic lesions. Significant expression differences were obtained for SPARC, MYC, and IGFBP1 in the peritoneal lesions and for MMP3 in the ovarian endometriomas. Additionally, significant differences were obtained for SPARC and IGFBP1 between the peritoneal and ovarian lesions. No significant differences were found for the studied genes between the control and the eutopic endometrium. CONCLUSION(S): This study identified 291 genes with differential expression in endometriotic lesions. The deregulation of the SPARC, MYC, MMP3, and IGFBPI genes may be responsible for the loss of cellular homeostasis in endometriotic lesions.
Fertil Steril. 2009 Feb 5. [Epub ahead of print]
Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants.
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
OBJECTIVE: We previously demonstrated that adherence of endometrial epithelial (EECs) and stromal cells (ESCs) to peritoneal mesothelial cells (PMCs) is partly regulated by ESC/EEC CD44 interactions with PMC associated hyaluronan. CD44, a transmembrane glycoprotein and major ligand for hyaluronan, has numerous splice variants which may impact hyaluronan binding. Here, we assessed whether ESCs and EECs from women with endometriosis demonstrate increased adherence to PMCs and examined CD44 splice variants’ potential role in this process. DESIGN: In vitro study. SETTING: Academic medical center. PATIENT(S): Fertility patients with and without endometriosis. INTERVENTION(S): Menstrual endometrium was collected from women with and without endometriosis confirmed surgically. The adherence of ESC/EECs to PMCs was measured. The ESC/EEC CD44 splice variants were assessed using dot-blot analysis. RESULT(S): The ESCs and EECs from women with endometriosis demonstrated increased adherence to PMCs. The predominant CD44 splice variants expressed by ESCs and EECs from women with and without endometriosis were v3, v6, v7, v8, v9, and v10. The ESCs and EECs from women with endometriosis were more likely to express v6, v7, v8, and v9. CONCLUSION(S): Increased eutopic endometrial-PMC adherence and CD44 splice variant expression may contribute to the histogenesis of endometriotic lesions. Elucidation of factors controlling this expression may lead to novel endometriosis therapies.
Fertil Steril. 2009 Feb 6. [Epub ahead of print]
Identification of novel peptides specifically binding to endometriosis by screening phage-displaying peptide libraries.
Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
OBJECTIVE: To search for novel peptides and common binding motif that specifically bind to endometriosis. DESIGN: Prospective study. SETTING: Department of Biological Science and Technology in national university. PATIENT(S): Specimens were divided into  ectopic endometrium (n = 10);  eutopic endometrium (n = 10). INTERVENTION(S): Peptides specifically binding to endometriosis are screened from a phage-displaying peptide library (Ph.D.-12) by using whole-cell screening technique after an adsorption elution amplification procedure. MAIN OUTCOME MEASURE(S): Combinatorial peptide libraries were used to identify small molecules that bind with high affinity to receptor molecules and mimic the interaction with natural ligands. Few pans of positive phage clones with significantly positive signals were identified by ELISA and analyzed by DNA sequencing. RESULT(S): During the biopanning processes, the recovered phage number (10(6) pfu/mL) in parts 1, 2, 3, 4, and 5 of the study were 9, 33, 82, 142, and 169. Nine phages consistently had residue Arg, whereas six clones had a consensus motif of Arg-X-Arg-X-X-X-X-Arg. The biotin-labeled peptide bound to endometriosis cells in a dose-dependent manner, yet the control peptide revealed lesser binding activity. CONCLUSION(S): The novel motif is associated with higher affinity of endometriosis, which might be useful in endometriosis targeting and as potential antiendometriosis therapies. We provide one potential approach for novel therapies toward endometriosis.
Fertil Steril. 2009 Feb 5. [Epub ahead of print]
Pelvic endometriosis and hydroureteronephrosis.
Chief of Urology Unit, I.R.C.C.S. Policlinico San Donato, University of Milan, Italy.
OBJECTIVE: To assess whether routine renal ultrasonography may be recommended in all patients with pelvic endometriosis, in order to avoid silent ureteral involvement of the disease. DESIGN: Retrospective descriptive study. SETTINGS: Tertiary center for the treatment of endometriosis at the Department of Obstetrics and Gynecology of the State University of Milan, Italy. PATIENT(S): Seven-hundred-fifty patients with a primary diagnosis of endometriosis, between January 2005 and July 2007. INTERVENTION(S): Routine urinary ultrasound; recording of patient history, signs, and symptoms; gynecologic examination; blood and urinary analyses; magnetic resonance imaging; spiral multislice computerized tomography. MAIN OUTCOME MEASURE(S): Symptoms and signs of ureterohydronephrosis; diagnosis of ureterohydronephrosis. RESULT(S): Twenty-three patients (3%) of all 750 patients with endometriosis had associated ureterohydronephrosis diagnosed at renal ultrasound. Symptoms secondary to ureteral and renal involvement were present in 10 patients (43.5%); 6 reported lumbar pain (26.1%) and 4 patients (17.4%) had renal colic. CONCLUSION(S): In our study, the high number (56.5%) of asymptomatic ureteral involvement in patients with known pelvic endometriosis seems to warrant the need for further investigations regarding the possibility to avoid the high percentage of silent renal losses. Unfortunately there appears to be no specific risk factor to allow for early suspicion nor a validated preventive diagnostic and therapeutic program. It remains to be evaluated whether urinary ultrasound ensures a beneficial cost-benefit ratio if employed on a routine basis.
Fertil Steril. 2009 Feb 5. [Epub ahead of print]
Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions.
Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, Erlangen, Germany.
OBJECTIVE: To investigate whether sexually transmitted viruses or prokaryotes, like human papilloma viruses (HPV), herpes viruses, and Chlamydia trachomatis, are associated with endometriosis lesions. DESIGN: Sixty-six endometriosis lesions from 56 patients, including 49 peritoneum, 16 ovarian, and one endometrium, were analyzed using polymerase chain reaction-based ELISA and Invader technology. Thirty control tissues including endometrium and peritoneum from patient-matched (n = 13) and patients without endometriosis (n = 13) and one cervical carcinoma were tested for HPV DNA. SETTING: University hospital. PATIENT(S): Seventy individual patients with and without endometriosis. INTERVENTION(S): Laparoscopy or laparotomy was performed, and endometriotic lesions were isolated. RESULT(S): Herpes viruses and Chlamydia trachomatis were not detected in endometriosis lesions. High-risk and medium-risk HPV were detected in 11.3% of lesions, corresponding to 13.2% of patients. In addition, 27.5% of control tissues were positive for HPV high and medium risk. One HPV18-positive ovarian endometriosis also associated with an ovarian carcinoma. Associating clinical history with HPV-positive endometriosis and control tissues, all patients had a prior HPV cervical infection. CONCLUSION(S): HPV infection in endometriosis lesions including control tissues supports spreading of the virus or HPV-infected endometrial cells via retrograde menstruation. Owing to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Feb;26(1):66-9.
Association of the CYP1B1 gene polymorphism with susceptibility to endometriosis
[Article in Chinese]
Department of Obstetrics and Gynaecology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011 PR China.
OBJECTIVE: To study the association between gene polymorphisms of cytochrome P450 1B1 (CYP1B1) in exon 2 codon 119 (G-T) and exon 3 codon 432 (C-G) and the susceptibility to endometriosis. METHODS: Allele-specific polymerase chain reaction was used to analyze the gene polymorphisms in 55 cases of endometriosis and 45 cases of normal controls. RESULTS: The frequencies of alleles G and T in codon 119 G/T of CYP1B1 gene showed a significant difference between the endometriosis group and the control group (P<0.05), with an odds ratio of 2.061. There was a significant difference in the frequencies of genotypes G/G, G/T and T/T between the two groups (P<0.05). Compared with wild-type G/G, the susceptibility of endometriosis with genotypes T/T and G/T was 2.625 and 3.214 fold, respectively. In the population with combined genotypes of CYP1B1 codon 119 GT or GG-codon 432 CC, statistically significant difference was observed between cases and controls (GT+CC vs GG+CC, OR=2.976, P<0.05). CONCLUSION: The gene polymorphisms of CYP1B1 in exon 2 codon 119 may be a genetic risky factor for endometriosis. The combination of CYP1B1 -GT and CYP1B1 -CC may act as a risky factor in the development of endometriosis.
J Mol Histol. 2009 Feb;40(1):53-8. Epub 2009 Feb 8.
C-fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action.
Laboratory of Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS CEP 90050-170, Brazil.
Endometriosis is an estrogen-dependent disease, causing pelvic pain and infertility. c-fos is an early transcription factor that has been reported to be related to estradiol-dependent cell proliferation. The aim of the present study was to assess the c-fos gene and protein expression in pelvic endometriotic implants in comparison to normal endometrium from infertile women. An open, prospective and controlled study included 15 infertile women with endometriosis and 19 control infertile women. Endometrial and endometriotic biopsies were performed at the follicular phase and the samples were processed for RT-PCR and immunohistochemistry. ERalpha mRNA levels were similar in the endometriotic implants/eutopic endometrium from women with endometriosis and in normal tissue (P = 0.649). The aromatase gene, however, was not expressed in the eutopic endometrium from either control or endometriosis groups, and was only expressed in 50% of endometriotic implants (P = 0.044). c-fos gene expression was higher in endometriotic implants (1.32 +/- 0.13; P = 0.011) than in eutopic endometrium from patients with endometriosis (0.97 +/- 0.11) or from the control group (0.91 +/- 0.05). In addition, immunohistochemistry showed a more abundant distribution of c-Fos in the stroma of endometriotic tissue compared to eutopic endometrium. These data suggest that c-fos may play a role in the molecular mechanisms of estrogen action on the induction, promotion or progression of endometriosis.
Environ Mol Mutagen. 2009 Jun;50(5):361-6.
Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis.
Department of Obstetrics and Gynaecology, Hebei Medical University, Shijiazhuang, China.
Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (-2578C/A, -1154G/A, -460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 174 adenomyosis patients and 199 frequency-matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the -2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42-0.97]. For the -1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33-0.80). However, the genotype distributions and allele frequencies of the -460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF -460/-1154/-2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41-1.00; OR = 0.44, 95% CI = 0.21-0.93, respectively). The study indicated that the -2578A or -1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development.
Reprod Sci. 2009 Apr;16(4):335-46. Epub 2009 Feb 5.
Priorities for endometriosis research: recommendations from an international consensus workshop.
Monash University, Melbourne, Australia. firstname.lastname@example.org
Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
Pathol Res Pract. 2009;205(9):653-6. Epub 2009 Feb 4.
Arias-Stella reaction as a diagnostic pitfall in a bladder biopsy with endometriosis: case report and review of the pseudoneoplastic bladder lesions.
Department of Pathology and Laboratory Medicine, Calgary Laboratory Services, University of Calgary, Alberta, Canada. email@example.com
Arias-Stella reaction is a hormone-induced atypical endometrial change that may involve endometrial, extraendometrial, or endometriotic sites. Establishing a correct diagnosis of Arias-Stella reaction may sometimes be problematic when seen outside of the uterine corpus, particularly in a limited biopsy sample when the pathologist is not aware of the clinical history. We report an Arias-Stella reaction in bladder endometriosis, which presented as a bladder mass in a 25-year-old pregnant woman. Clinical information of intrauterine pregnancy (week 16) was not initially provided when the biopsy was performed. We also discuss endometriosis, endocervicosis, and müllerianosis of the bladder, which are benign glandular lesions that may mimic tumors within the bladder wall.
World J Gastroenterol. 2009 Feb 7;15(5):612-4.
Intestinal endometriosis–a rare cause of colonic perforation.
Eastbourne Hospital, Eastbourne, East Sussex BN21 2UD, United Kingdom.
Endometriosis is the ectopic growth of viable endometrium outside the uterus, affecting approximately 7% of females. It commonly affects pelvic structures including the bowel. Perforation of the colon by endometriosis is very rare and the patients generally present with an asymptomatic or painful pelvic mass, often in the left iliac fossa. Our patient presented acutely unwell and her symptoms were more suggestive of pyelonephritis or diverticulitis. We therefore report an unusual cause of acute abdomen. The purpose of the following case report is to elucidate certain diagnostic and therapeutic problems of the disease, concerning both surgeons and gynaecologists. In summary, intestinal endometriosis should be considered in the differential diagnosis of all post-menarche women with episodic gastrointestinal symptoms. A past history of endometriosis or co-existent gynaecological symptoms should increase the index of suspicion, and laparoscopy prior to formal laparotomy should be considered. Our patient, in retrospect, had a history of mild endometriosis, but we feel that this case serves as a reminder of a rare, but important, differential diagnosis of acute abdomen in females.
Maturitas. 2009 Mar 20;62(3):270-5. Epub 2009 Feb 3.
Diverse molecular pathways in ovarian cancer and their clinical significance.
Discipline of Obstetrics and Gynaecology, Research Centre for Reproductive Health, Adelaide University, Adelaide, Australia.
The origin of epithelial ovarian cancer remains unknown. It is believed to develop from ovarian surface epithelium, post-ovulatory inclusion cysts, endometriosis and more recently the fimbrial end of the fallopian tube. Molecular evidence suggests that ovarian cancer may progress both through a step-wise mutation process (low-grade pathway, type I), and a separate pathway with high genetic instability leading to rapid metastasis without an identifiable precursor lesion (high-grade pathway, type II). This sub-classification explains the clinical and biological heterogeneity of ovarian cancer and highlights the importance for developing novel diagnostics and therapeutics targeting two unique diseases-type I and type II ovarian carcinomas. This article summarises current knowledge of the aetiology and molecular basis of ovarian cancer and discusses recent clinical strategies for type I and type II disease.
Reprod Biomed Online. 2009 Feb;18(2):282-9.
Outcome after multidisciplinary CO2 laser laparoscopic excision of deep infiltrating colorectal endometriosis.
Leuven University Fertility Centre, Department of Obstetrics and Gynecology, University Hospital Leuven, Belgium.
The aim of this retrospective cohort study was to evaluate clinical outcome after multidisciplinary laparoscopic excision of deep endometriosis. Patients (n = 56) were asked to complete questionnaires regarding quality of life (QOL), pain, fertility and sexuality to compare their status before and after surgery, and their medical files were analysed. Statistical analysis was performed with life table analysis, paired Wilcoxon and McNemar tests. Gynaecological pain, QOL and sexual activity improved significantly (P < 0.001; P < 0.0001 to P = 0.008 and P < 0.0001 to P = 0.0003 respectively) during a median follow-up 29 months after surgery. Post operative complications occurred in 11% but were directly related to surgery in only 5%. The cumulative recurrence rate of endometriosis was 2 and 7% at 1 and 4 years after surgery respectively. Cumulative pregnancy rate was 31 and 70% at 1 and 4 years after surgery respectively. In conclusion, multidisciplinary CO(2) laser laparoscopic excision of deep endometriosis with colorectal extension improves pain, QOL and sexuality with high fertility and low complication and recurrence rates.
Reprod Biomed Online. 2009 Feb;18(2):167.
Is operative laparoscopy safe in ovarian endometriosis?
Gynecologic Endocrinology Unit, Civitanova Marche Hospital, Civitanova Marche (MC) 62012 Italy. firstname.lastname@example.org
This short communication describes the delayed onset of premature ovarian failure (POF) in some young patients, between 5 to 24 months after operative laparoscopy for ovarian endometriosis. This complication apparently does not have a link with traditional risk factors for POF. In view of this observation, further and consistent clinical investigations are necessary to seek an explanation for this possible iatrogenic effect, which is of particular concern to young patients who are referred for video laparoscopy as a treatment for ovarian endometriosis.
World J Surg. 2009 Apr;33(4):822-7.
Anatomic significance of a positive barium enema in deep infiltrating endometriosis of the large bowel.
Department of Gynecology, Academic Hospital Erasme, Free University of Brussels (ULB), 808, Route de Lennik, 1070, Brussels, Belgium. email@example.com
PURPOSE: The anatomopathological significance of a positive double-contrast barium enema (DCBE) for suspicion of deep infiltrating endometriosis of the large bowel was studied. This is a retrospective study of a prospective database. METHODS: A large-bowel resection was proposed for patients who were suspicious for large-bowel endometriosis and had a positive DCBE. In a series of 73 patients, 71 large-bowel resections were performed. Histology and immunohistochemistry with the monoclonal antibody CD-10 were performed on the resection specimen. Outcome measures were the length of the resected specimen, the largest diameter of the lesion, the positivity of the resection margins, and the degree of infiltration of the large bowel. We also compared the mean largest diameters of the lesions with the degree of infiltration of the large bowel. RESULTS: Between December 1997 and October 2005, 80 patients were suspicious for large-bowel endometriosis: 73 (91%) had positive DCBEs, and 7 (9%) had negative DCBEs. Of the 73 with positive DCBEs, 4 (5%) refused digestive resection and 1 (1.4%) was excluded. Three patients underwent two large-bowel resections because of the presence of bifocal lesions (left and right colon). A total of 71 resections were performed. In case of positive DCBE, the perivisceral fat and the whole muscularis were infiltrated in 100% of cases. The infiltration reached the submucosa and the mucosa respectively in 82% and 18% of cases. A total of 9.9% of resection margins were positive at histology but only focally. The mean largest diameter of the lesions infiltrating the whole thickness of the large bowel was not statistically different from the mean largest diameter of more superficial lesions. CONCLUSIONS: Findings of mass effect with indentations and ridging of the mucosa on DCBE in a setting suspicious for large-bowel endometriosis correspond well with pathologic findings of deep infiltration of the large-bowel wall. Clinicians dealing with deep infiltrating endometriosis should be aware of these findings, which could influence their choice of surgical treatment.
Hum Reprod. 2009 May;24(5):1025-35. Epub 2009 Feb 3.
Dopamine agonist administration causes a reduction in endometrial implants through modulation of angiogenesis in experimentally induced endometriosis.
Instituto Valenciano de Infertilidad (IVI), University of Valencia, Plaza de la Policía Local, 3, 46015 Valencia, Spain.
BACKGROUND: Implantation of a retrogradely-shed endometrium during menstruation requires an adequate blood supply. The endometrium has angiogenic potential, and endometriotic lesions grow in areas with a rich vascularization, suggesting that angiogenesis is a prerequisite for endometriosis development. Targeting vascular endothelial growth factor (VEGF) leads to an inhibition of endometriosis. Dopamine and its agonists, such as cabergoline (Cb2), promote VEGF receptor-2 (VEGFR-2) endocytosis in endothelial cells, preventing VEGF-VEGFR-2 binding and reducing neoangiogenesis. The aim of this study was to evaluate the anti-angiogenic properties of Cb2 on growth of established endometriosis lesions and investigate the molecular mechanisms by which Cb2 exerts the anti-angiogenic effect. METHODS: Human endometrium fragments were implanted in female nude mice peritoneum, and mice were treated with vehicle, 0.05 or 0.1 mg/kg/day oral Cb2 for 14 days. After treatment, the implants were processed to assess proliferative activity, neoangiogenesis, VEGFR-2 phosphorylation and angiogenic gene expression. RESULTS: A significant decrease in the percentage of active endometriotic lesions (P < 0.05) and cellular proliferation index (P < 0.001) was found with Cb2 treatment. Neoangiogenesis was reduced by Cb2 treatment, as observed at gross morphological level and by significant changes in gene expression. The degree of VEGFR-2 phosphorylation was significantly lower in Cb2-treated animals than controls. CONCLUSIONS: Cb2 treatment in experimental endometriosis has an anti-angiogenic effect acting through VEGFR-2 activation. These findings support the testing of dopamine agonists as a novel therapeutic approach to peritoneal endometriosis in humans.
Int J Gynecol Pathol. 2009 Mar;28(2):114-9.
A pilot evaluation of a novel immunohistochemical assay for topoisomerase II-alpha and minichromosome maintenance protein 2 expression (ProEx C) in cervical adenocarcinoma in situ, adenocarcinoma, and benign glandular mimics.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
The histopathologic distinction of cervical adenocarcinoma in situ (AIS) and invasive adenocarcinoma (AC) from some benign endocervical lesions can be challenging. The ProEx C antibody reagent targets nuclear proteins (minichromosome maintenance protein 2, MCM2 and topoisomerase II-alpha, TOP2A), which are over expressed during the aberrant S-phase induction of HPV infected and neoplastic cells. In this immunohistochemical study the utility of the ProEx C reagent in distinguishing AIS and AC from a variety of non-neoplastic glandular lesions was examined. ProEx C immunohistochemical staining was performed on sections from formalin-fixed, paraffin-embedded tissue of 65 cervical tissues including 48 non-neoplastic cervices (normal [n=10], microglandular hyperplasia [n=10], tubal metaplasia [n=11], cervical endometriosis [n=7], reactive endocervix [n=10]) and 17 cervices with glandular malignancy (AIS [n=12] and AC [n=5]). Both intensity and prevalence of immunoreactivity was scored. The median and distribution of scores for both prevalence and intensity was compared for AIS versus each of the 5 benign cervical lesions using a Mann-Whitney U test. The median and distribution of prevalence of immunohistochemical staining for AIS was different from all benign mimics, but the intensity of staining for AIS did overlap with some mimics as it was not significantly different from endometriosis, microglandular hyperplasia, and reactive endocervix. ProEx C reagent has potential as an adjunctive testing tool in the histopathologic diagnosis of both AIS and AC, particularly in difficult cases with small biopsies or foci of disease.
Int J Gynecol Pathol. 2009 Mar;28(2):148-56.
Expression of cyclooxygenase-2 and matrix metalloproteinase-2 in adenomyosis and endometrial polyps and its correlation with angiogenesis.
Departments of Pathology, Afyonkarahisar Kocatepe University School of Medicine, Afyonkarahisar, Turkey. firstname.lastname@example.org
This study investigates the expression of cyclooxgenase (COX)-2 and matrix metalloproteinase (MMP)-2 in patients with adenomyosis or endometrial polyps and their possible relation to microvascular density in these lesions. The subjects were 25 patients with adenomyosis, 30 patients with endometrial polyps, and 20 female controls. The expression of COX-2, MMP-2, and CD34 was studied immunohistochemically. Microvesseldensity (MVD) was calculated by the counting of CD34-positive vascular endothelial cells. The quantity and intensity of COX-2 expression in endometrium did not vary during the menstrual cycle in the control group and in patients with endometrial polyps. In patients with adenomyosis, it was higher in the secretory phase. MMP-2 expression in stromal cells in adenomyotic foci and endometrial polyps were higher than in normal endometrium. In the proliferative phase, MVD in adenomyosis foci was higher than in normal endometrium and endometrial polyps. In the secretory phase, MVD in adenomyotic foci and endometrial polyps was higher than in normal endometrium. Overexpression of stromal MMP-2 may play a role in the development of adenomyosis and endometrial polyps. Aberrant COX-2 expression in eutopic endometrium during the luteal phase may be associated with the pathogenesis of adenomyosis; however, expression of COX-2 does not seem to play a role in the development of endometrial polyps. MVD was high in both lesions, but there was no significant correlation between MVD and the expression of MMP-2 or COX-2. Mechanisms other than COX-2 and MMP-2 may contribute to the promotion of angiogenesis in these lesions.
Int J Gynecol Pathol. 2009 Mar;28(2):157-63.
Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha), and microvessel density in endometrial tissue in women with adenomyosis.
Anatomia Patologica, Dipartimento di Neuroscienze, Università Politecnica delle Marche, Ospedali Riuniti di Ancona-Torrette, Via Conca 71, 60020 Torrette di Ancona, Italy. email@example.com
Adenomyosis is a disease with a mysterious pathogenesis, defined by an abnormal displacement of the eutopic endometrium deeply and haphazardly inside the myometrium. Angiogenesis has been indicated to play an important role and our aim was to investigate whether vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) expression and microvessel density (MVD) were different in women with and without adenomyosis. Immunohistochemistry was performed in endometrial tissues in 23 patients who underwent radical hysterectomy for adenomyosis (14) and for ovarian cysts and fibroids (9) at an Academic Hospital. Compared to women without the disease, VEGF expression was increased in endometrium with a normal location in patients with adenomyosis, although not associated to a significant increase of HIF-1alpha and MVD. Moreover, the endometrium with an abnormal location in patients with adenomyosis showed an increased VEGF and HIF-1alpha expression, particularly in the epithelial cells, associated to an increase of MVD, compared with the endometrium in a normal location in the same group of patients. Our present findings suggest that VEGF-mediated angiogenesis might be associated with the development of adenomyosis. In the ectopic foci the abnormal location might contribute to increased HIF-1a expression, stimulation of VEGF production, and increased vessel formation. In endometrium with a normal location, instead, where VEGF increased expression seems not to be correlated with HIF-1alpha increased expression nor with an increased MVD, other mechanisms might be reasonably postulated. Additional studies are required to explore new targeted and more effective treatment modalities.
Int J Gynecol Pathol. 2009 Mar;28(2):193-6.
Ovarian and paraovarian squamous-lined cysts (epidermoid cysts): a clinicopathologic study of 18 cases with comparison to mature cystic teratomas.
Department of Pathology and Laboratory Medicine, Washington Hospital Center, Washington, DC 20010, USA.
The origin of ovarian epidermoid cyst is unknown. Sixteen ovarian and 2 paraovarian squamous-lined cysts unassociated with teratomatous elements were studied. The ovarian cysts represented 1.5% of consecutive ovarian surface epithelial tumors examined and were one-nineteenth as common as mature cystic teratoma. The mean patient age was 57 years. All tumors were unilateral and the majority were incidental findings. The mean tumor size was 1.75 cm and the median, 3.0 cm. In comparison to 120 consecutive patients with mature cystic teratoma who had a mean age of 41 years and a mean tumor size of 6 cm, the ovarian epidermoid cysts were significantly smaller and occurred at a significantly older age (P<0.01). All cysts displayed mature squamous epithelium with a granular layer, with hyperkeratosis in 14 and parakeratosis in 4. In 2 patients, there were contralateral mature cystic teratomas, and in 2 others the cysts contained rare hairs. Two displayed foci of Brenner tumor and 1 appeared to arise in endometriosis. In summary, 7 of 16 ovarian epidermoid cysts displayed features suggesting they reflected insufficiently sampled teratomas, Brenner tumors with squamous metaplasia, or a metaplastic change in endometriosis. Epidermoid cyst of the ovary as defined by histology is a heterogeneous group; pure epidermoid cyst, if it exists at all, probably represents less than 1% of ovarian surface epithelial tumors.
BJOG. 2009 Feb;116(3):366-71.
‘Blood On The Tracks’ from corpora lutea to endometriomas.
Università degli Studi di Milano, Milan, Italy. firstname.lastname@example.org
OBJECTIVE: To detect a direct transition from a haemorrhagic corpus luteum to an endometriotic cyst by serial transvaginal ultrasonographic scans. DESIGN: Prospective observational study. SETTING: An academic tertiary care and referral centre for women with endometriosis. POPULATION: One hundred and nine women younger than 40 years, with regular menstrual cycles, undergoing first-line surgery for endometriomas, and not wanting postoperative oral contraception. METHODS: Three-monthly transvaginal ultrasonography during the luteal phase for 2 years after surgery. MAIN OUTCOME MEASURE: Sonographic identification of progression from a haemorrhagic corpus luteum to a recurrent endometriotic cyst. RESULTS: A haemorrhagic corpus luteum was identified in 13 women. Serial ultrasonographic scans demonstrated transition to an endometriotic cyst in 11 (85%) instances and resorption in two. A unilateral endometriotic cyst without previous detection of a cystic corpus luteum was observed in 14 women. CONCLUSIONS: Bleeding from a corpus luteum appears to be a critical event in the development of endometriomas.
Contraception. 2009 Mar;79(3):189-93. Epub 2008 Dec 11.
The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis.
Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
BACKGROUND: The objective of this study was to evaluate the efficacy and side effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of moderate or severe dysmenorrhea associated with adenomyosis for a 3-year follow-up period. STUDY DESIGN: The LNG-IUS was inserted into 94 women who had moderate or severe dysmenorrhea associated with adenomyosis diagnosed by transvaginal sonography during Cycle Days 5-7. A visual analogue scale (VAS) of dysmenorrhea, uterine volume and serum CA125 levels were used to assess the efficacy of the treatment at baseline and 3, 6, 12, 24 and 36 months after the LNG-IUS insertion. Side effects were recorded at every follow-up visit. RESULTS: The VAS of dysmenorrhea dropped continuously and significantly from the baseline score of 77.9+/-14.7 to 11.8+/-17.9 after 36 months of the LNG-IUS insertion (p<.001). The uterine volume decreased significantly from 113.8+/-46.9 mL to 94.5+/-40.1 mL (p=.003) at 6 months and to 87.7+/-35.8 mL (p<.001) at 12 months and then rose slightly, but the variables at 24 and 36 months still decreased significantly in comparison with the baseline variable (p<.001). The serum CA125 levels reduced significantly starting from 6 months after device insertion (p<.001). The most common side effects were weight gain (28.7%), simple ovarian cyst formation (22.3%) and lower abdominal pain (12.8%). At 36 months, the overall satisfaction rate of the treatment was 72.5%. CONCLUSIONS: The LNG-IUS appears to be an effective method in alleviating dysmenorrhea associated with adenomyosis during 3 years. It may be a valuable long-term alternative for the treatment of adenomyosis.
Cardiovasc Intervent Radiol. 2009 Jan 30. [Epub ahead of print]
Radiofrequency Ablation of Abdominal Wall Endometrioma.
Varese, Italy, email@example.com.
Extraperitoneal endometriosis is the presence of ectopic, functional endometrium outside the peritoneal cavity, and its occurrence is exceedingly rare. Diagnostic imaging-including ultrasound, duplex ultrasonography, and magnetic resonance imaging-in the preoperative assessment of patients with suspected abdominal wall endometriosis (AWE) is helpful for detection and accurate determination of the extent of disease. The treatment of choice for AWE is surgical excision. In addition, medical therapies can be used. We present one case of AWE treated with percutaneous radiofrequency ablation under ultrasound guidance. There were no major complications, and the patient’s symptoms improved. In selected patients, radiofrequency ablation can be used safely for the treatment of AWE; however, further studies are needed to confirm this hypothesis.
Eur J Obstet Gynecol Reprod Biol. 2009 Apr;143(2):128-9. Epub 2009 Jan 31.
A 3-year follow-up of women with endometriosis and pelvic pain users of the levonorgestrel-releasing intrauterine system.
Ther Umsch. 2009 Feb;66(2):129-35.
Does hormonal contraception increase the risk for tumors?
[Article in German]
Poliklinik für gynäkologische Endokrinologie und Reproduktionsmedizin, Universitätsklinikum Hamburg-Eppendorf. firstname.lastname@example.org
A non-contraceptive benefit of oral hormonal contraceptives (OC) is a diminished risk for certain benign as well as malignant tumours, such as benign breast tumours, uterine fibroids and ovarian cysts. Endometriosis itself is not positively influenced by OC, but dysmenorrhea is decreased. Modern low-dose OC do not increase the risk of liver cell adenomata or carcinomata. OC do not influence melanoma. Modern data do not suggest an increased risk for breast carcinoma in OC users. Long-term use of OC leads to a decreased risk of endometrial and colorectal carcinomata. Cervical carcinoma is not influenced directly by OC, but probably indirectly through a change in sexual behaviour. There is no increase of vulvar or vaginal carcinoma, even after long-term use of OC.
Ther Umsch. 2009 Feb;66(2):101-8.
Long-cycle treatment in oral contraception
[Article in German]
Universitätsklinik für Gynäkologie und Frauenheilkunde, J. W. Goehte-Universität, Frankfurt. H.Kuhl@em.uni-frankfurt.de
Surveys show that most women desire a change in their menstrual pattern in the sense that they would prefer less menstruations or even amenorrhea. On this behalf, there is no difference between women having spontaneous natural cycles and women taking the pill. The main reasons are less menstrual bleedings, better hygienic conditions, a better quality of life and less blood loss. In women wanting regular monthly periods, the opinion is dominant that suppression of menstrual bleedings is “unnatural”. It is therefore primordial to inform women that contraceptive safety is even increased in users following the long-cycle principal and that a fertility decrease has not to be feared. The benefit of the long-cycle OC is a reduction of the hormonal fluctuations induced by the pill-free interval with its consecutive somatic and mental symptoms, as well as an increased contraceptive safety. The following cycle- and menstruation-dependent symptoms as listed as an indication for the long-cycle use: Endometriosis, hypermenorrhea, dysmenorrhea, hemorrhagic diathesis, uterine fibroma, polyzystic ovary syndrome, migraine due to estrogen-deficiency in the pill-free interval as well as premenstrual syndrome.
Clin Obstet Gynecol. 2009 Mar;52(1):2-20.
Imaging of acute pelvic pain.
Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, Maryland, USA. email@example.com
Determining the cause of acute pelvic pain in the female patient is often a clinical challenge. Diagnostic imaging can be invaluable in this situation. Ectopic pregnancy, pelvic inflammatory disease, and hemorrhagic ovarian cysts are the most commonly diagnosed gynecologic conditions presenting with acute pelvic pain. Ovarian torsion and degenerating fibroids occur less frequently. Other causes to consider include endometriosis, and postpartum causes such as endometritis, or ovarian vein thrombosis. Finally, nongynecologic conditions may overlap in their presentation of acute pelvic pain and should also be considered. The most important of these is acute appendicitis.
Orv Hetil. 2009 Feb 8;150(6):245-50.
Endometriosis[Article in Hungarian]
Debreceni Egyetem, Orvos- és Egészségtudományi Centrum, Altalános Orvostudományi Kar, Szülészeti és Nogyógyászati Klinika, Debrecen.
Endometriosis (ectopic endometrial tissue) is a benign condition with many symptoms (e.g., infertility dysmenorrhoea, pelvic pain) and may lead to serious complications. It affects women of reproductive age, however, in rare cases it may also develop before menarche. The estimated frequency of endometriosis used to be 1-2%, but since the advent of laparoscopy it has increased to 6-10%. Direct spread (e.g., in endometriosis interna seu adenomyosis), retrograde menstruation, embolisation, metaplasia together with defective immunological and genetic processes have all been confirmed as possible mechanisms of the development of disease. Laparoscopy plays a leading role in the diagnosis, however, physical examination and imaging techniques (e.g., sonography) remain an essential part of preoperative assessment. The treatments of endometriosis include various endocrine manipulations, surgery and palliation.