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PubMed2001

Induction of endometriosis in the mouse inhibits spleen leukocyte function.

BACKGROUND: It is still unclear whether the immunologic perturbation observed in women with endometriosis represents an intrinsic defect of the immune system or it is consequent to the presence of endometrium in ectopic sites. The present study was aimed to evaluate the immunoregulatory properties of ectopic endometrial implants in a model of experimental endometriosis in mice. METHODS: Endometriosis was induced in n=10 mice by inoculating endometrial fragments obtained from syngenic donor mice into the peritoneal space. Twelve mice were similarly treated but were not inoculated with endometrium and were used as control mice. At an explorative laparotomy performed in all the animals after three weeks, the extent of peritoneal lesions, when present, was evaluated by weight assessment and surface area measurement. In both mice that were inoculated with endometrium and control animals, spleens were removed. The effect of endometriosis induction on concanavalin A-induced spleenocyte proliferation was investigated. RESULTS: A significant inhibition of spleenocyte growth was demonstrated in mice in which endometriosis was induced (36156+/-3061 cpm) compared to control animals (47172+/-3210 cpm; p<0.05). Moreover, a significant inverse correlation was found between spleenocyte proliferation and weight and surface area of the peritoneal endometriotic lesions (r=0.76; p<0.02 and r=0.75; p<0.02, respectively). CONCLUSION: These findings suggest that the presence of ectopic endometrial implants within the peritoneal cavity leads to substantial changes of the immune response in vivo. These changes may have significant implications for the understanding of the etiopathogenesis of endometriosis.

Animals↗

PubMed2001

Mouse embryo toxicity of IL-6 in peritoneal fluids from women with or without endometriosis.

BACKGROUND: To determine whether there is a factor (or factors) in the peritoneal fluid of endometriosis patients that impairs embryo growth and embryo implantation. METHODS: Growth and development of two-cell mouse embryos which were cultured in media with peritoneal fluid from women with or without endometriosis and interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels in conditioned media were measured. RESULTS: The blastocyst rate in the non-endometriosis group was 46.4 +/- 31.1%, and that of the endometriosis group was 54.6 +/- 28.7%. Logistic regression analysis using the criteria of blastocyst development in 454 embryos, showed that the peritoneal fluid from endometriosis could promote (p=0.015) but IL-6 could arrest embryo growth to blastocyst (p=0.025). IL-1beta and TNF-alpha levels had no significant effect on blastocyst formation. CONCLUSION: Peritoneal fluid from women with endometriosis was not toxic to mouse embryo development. However, IL-6 in the peritoneal fluid deteriorated the growth and development of mouse embryos.

Adult↗

PubMed2002

Increased expression of cyclooxygenase-2 in local lesions of endometriosis patients.

PROBLEM: Human endometrial glands contain the highest levels of cyclooxygenase (COX), although whether it is COX-1 and/or COX-2 has not been previously determined. Overexpression of COX-2 may result in the pathogenesis of endometriosis. METHOD OF STUDY: Tissue sections were obtained from 28 premenopausal women undergoing laparotomy or laparoscopic surgery for benign conditions. Endometrium, ectopic endometriosis tissue and peritoneum were obtained at the time of surgery. Informed consents were obtained from all the patients participating in this study. Immunohistochemistry was performed on consecutive sections of paraffin-embedded tissue using anti-COX-2 antibody. Expressions of COX-2 mRNA in endometrium, ectopic endometriosis tissue, and peritoneum were quantitavely determined by competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the uterus, COX-2 was localized in the endometrial epithelium. Eutopic endometrial surface epithelium contains more COX-2 than does glandular epithelium. We observed more frequent and denser COX-2 staining in the ectopic endometriosis implants when compared with eutopic endometrium. Level of COX-2 mRNA in endometriosis was increased up to five times that of eutopic endometria. CONCLUSION: Hyper activation of COX-2 with abnormal prostaglandin generation is considered to contribute to the pathophysiology of endometriosis and disease progression.

Adult↗

PubMed2003

Increased production of tumor necrosis factor-alpha by peritoneal fluid mononuclear cells induced by 60-kDa heat shock protein in women with minimal to mild endometriosis.

PROBLEM: We sought to examine the role of Hsp60, a 60-kDa stress-responsive protein (hsp60) with potent immunostimulatory properties, in the pathophysiology of endometriosis. We investigated the response of peritoneal fluid mononuclear cells (PFMCs) to hsp60 to identify differences in PFMCs between women with and without endometriosis. METHOD OF STUDY: PFMCs from women with or without endometriosis were incubated with hsp60 in vitro. The release of tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The rapid secretion of TNF-alpha was observed following the exposure of PFMCs to hsp60. PFMCs from women with minimal to mild endometriosis produced greater amounts of TNF-alpha in response to hsp60 stimulation than levels seen in cells from women without endometriosis. CONCLUSION: Hsp60 may play a role in the activation of peritoneal immunity in patients with minimal to mild endometriosis.

Adult↗

PubMed2000

Smooth muscle metaplasia in ovarian endometriosis.

AIMS: Little is known about smooth muscle metaplasia (SMM) in ovarian endometriosis. The clinicopathological significance of SMM in ovarian endometriosis is analysed. METHODS AND RESULTS: Three hundred and twenty-seven consecutive cases of ovarian endometriosis, including 58 cases associated with malignant ovarian epithelial tumour, between 1987 and 1996 were retrieved from hospital files and clinicopathologically analysed. The ages of the patients who showed SMM in ovarian endometriosis ranged from 28 to 70 years (average, 43. 8 years). SMM was observed in 58 cases (17.7%); in 51 of 269 cases without tumour (19.0%) and in seven of 58 with tumour (12.1%). The differences in the incidence of SMM in cases with and without tumour were not statistically significant. SMM was a focal, microscopic change and there was neither smooth muscle tumour nor uterus-like mass. Sixteen cases had short fascicles or stellate foci of SMM in the endometriotic stroma, an incomplete rim of SMM surrounding the endometriotic cysts was present in 32 cases, and 10 cases showed SMM in both the endometriotic stromal and incomplete rim of the endometriotic cysts. There was no significant histological difference in SMM between cases with and without malignant ovarian epithelial tumour. CONCLUSIONS: SMM in ovarian endometriosis is not an uncommon phenomenon. SMM may be explained in two ways. First, smooth muscle originates from metaplastic endometrial stromal cells in endometriotic foci. Second, it originates from metaplastic ovarian stromal cells in the rim of endometriosis.

Adult↗

PubMed2000

Rectosigmoid endometriosis: endoscopic ultrasound features and clinical implications.

BACKGROUND AND STUDY AIMS: The main area of the gastrointestinal tract affected by deep pelvic endometriosis is the rectosigmoid colon in 3-37% of cases. Due to the risk of infiltration and the clinical symptoms of endometriosis, with pain and infertility, the condition may require surgical resection. Preoperative imaging diagnosis of rectosigmoid involvement is therefore important. Rectal endoscopic ultrasonography (EUS), which is already used for the staging of anorectal carcinoma and submucosal lesions, may be a promising technique for this indication. The present study was conducted in order to describe the endosonographic appearance of rectosigmoid endometriosis, and to define the potential relevance of the technique to the choice of resection method. PATIENTS AND METHODS: Between 1993 and 1997, 46 women (mean age 31) with deep pelvic endometriosis underwent imaging investigations and surgical resection. The clinical and imaging findings, and the surgical and histological features identified--mainly with regard to infiltration of the rectal wall--were compared retrospectively. The impact of the EUS findings on the decision on whether or not to carry out resection, either by laparoscopy or open abdominal surgery, was also examined. RESULTS: When there was deep pelvic endometriosis with suspected rectal wall infiltration, EUS showed normal anatomy in nine patients, endometriotic lesions without rectal wall infiltration in 12, and typical rectal infiltration in 25. The lesions were confirmed by the surgical findings during therapeutic laparoscopy (n = 22) and laparotomy (n = 25), as well as by clinical follow-up. Rectal wall infiltration, demonstrated in all cases using EUS, had initially been suspected on the basis of clinical examinations, rectoscopy, barium enema, computed tomography, and magnetic resonance imaging in 62%, 50%, 33%, 67% and 66% of cases, respectively. CONCLUSIONS: EUS is a simple and noninvasive technique capable of correctly diagnosing rectal wall infiltration in deep pelvic endometriosis. It may be helpful in determining the choice between laparoscopy and laparotomy when complete resection is indicated.

Adult↗

PubMedDate not supplied

[Psychosomatic aspects of endometriosis].

Endometriosis is a varied and unspecific disorder, which can be detected by way of subtle diagnostics in almost every woman. In one case it is a minor accidental finding, in another case it is a cancer-like, mostly incurable, chronic painful a disease, which often has sterility and aggressive therapies as subsequence. For the origin of endometriosis many causes are discussed. The theory of retrograde menstruation through an hyperperistaltic-dystocic uterus presents on one hand an organic explanation-concept. From the psychosomatic point of view this unphysiological menstruation could also be seen as the result of an unsolved conflict, which might be connected with the gender-role or personal, familiar and social attitudes about menstruation. The exo- and endogenic supply with hormones in a time with less pregnancies and therefore more menstruation is also a contributing factor to the origin and development of this disturbance. Beside the theory of endometriosis as an autoimmune disease also implicates psychosomatic thoughts. Though there is always a repeatedly talk the "cancer of the career-woman", there are however very few psychosomatic research projects regarding endometriosis. Therefore it is a characteristic of this disease, that finding and feeling are very often controversial. This emphasizes the importance of psychosomatic, psychosexual, social and biographical aspects in connection with endometriosis. This point of view makes a relative plausible and comfortable explanation for the CPPS and sterility uncertain. Without question diagnosis and therapy of endometriosis followed on one hand by stigmatization and on the other hand by often restriction of quality of life leads to a lot of subsequent psychosocial problems.

Endometriosis↗

PubMed2005

[Endometriosis and adenomyosis].

Peristaltic activity of the non-pregnant uterus serves fundamental functions in the early process of reproduction. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have an increased potential of implantation and proliferation resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of about 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. The principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary thus resulting in hyperperistalsis. Minimal endometriosis of the fertile women, endometriosis and adenomyosis of the infertile women and adenomyosis of the parous peri- and postmenopausal women are considered as phenotypes of a pathophysiological continuum with uterine peristalsis playing a prominent role.

Endometriosis↗

PubMed2005

Value of endorectal ultrasonography for diagnosing rectovaginal septal endometriosis infiltrating the rectum.

BACKGROUND AND STUDY AIMS: Rectovaginal septal endometriosis (RVSE) can pose serious therapeutic problems when there is infiltration of the rectal septum (which occurs in approximately half of the cases). The aim of this study was to assess the value of endoscopic ultrasonography in diagnosing rectal wall involvement by pelvic endometriosis. PATIENTS AND METHODS: A prospective study was carried out from May 1998 to March 2003 at a single hospital center. The 30 patients included in the study presented with suspected RVSE and underwent systematic anorectal endoscopic ultrasonographic exploration prior to the surgical intervention. The endoscopic ultrasonography was carried out under general anesthesia with a 7.5-MHz miniprobe equipped with a distal balloon. RESULTS: The anorectal endoscopic ultrasonographic examination (EUS) showed the presence of endometriosis in the rectovaginal septum in 26 patients (88 %), in the uterosacral ligaments in 10 patients (33 %), and in the ovaries in two patients (6 %). At EUS, the nodules were infiltrating the rectal wall in 17 patients (56 %). The surgical exploration demonstrated endometriosis in the rectovaginal septum in 26 cases, the uterosacral ligaments in 22 cases, and the ovaries in 16 cases. The rectal wall was completely infiltrated in 12 cases and only partly in four cases, and intestinal tract resection was required in 10 cases. The sensitivity, specificity, and positive and negative predictive value of anorectal endoscopic ultrasonography as a means of diagnosing endometriosis of the rectovaginal septum and infiltration of the rectal wall were found to be 96 %, 100 %, 100 % and 83 %, and 92 %, 66 %, 64 % and 92 %, respectively; and the diagnostic accuracy was at 96 % and 80 %, respectively. The sensitivity for detecting nodules in the uterosacral ligaments or in the ovaries was 42 % and 14 %, respectively, leading to diagnostic accuracy rates of 56 % and 53 %. CONCLUSIONS: In terms of its sensitivity and its negative predictive value, anorectal endoscopic ultrasonography is a very effective means of detecting endometriosis of the rectovaginal septum and assessing possible infiltration of the rectal wall. However, this method is not as accurate for nodules located far from the EUS probe, as is the case with the uterosacral ligaments and ovaries.

Adult↗

PubMed2001

Surgically induced endometriosis attenuates accrual of bone mineral density in growing rats.

OBJECTIVE: A possible association of endometriosis with decreased bone mineral density in women has been proposed. It has been reported that cortical and trabecular bone mass of the distal portion of the radius is decreased in patients with endometriosis. The objective of this study was to investigate the relationship between endometriosis and bone mineral density with the use of a rat model. STUDY DESIGN: Cycling female Sprague-Dawley rats (180 days old) were randomly assigned to 1 of 2 groups. The treatment group (n = 16) underwent surgical induction of endometriosis. Female rats (n = 17) with surgically transplanted abdominal muscle served as control animals. Dual-energy x-ray absorptiometry measurements were obtained before surgery and after 90 days with a Lunar DPX-MD+ (GE Lunar, GE Medical Systems, Milwaukee, Wis) bone densitometer, with software standardized for small animal research. RESULTS: Experimental animals had grossly visible endometriotic disease at necropsy (90 days). The mean net change in total bone mineral density from baseline to 90 days in the control group was +0.019 +/- 0.002 g/cm2, whereas the mean net change in total bone mineral density for the experimental group was +0.013 +/- 0.002 g/cm2. The experimental group gained less bone than the control group (P = .02). CONCLUSION: The age-appropriate increase in bone mineral density known to occur in this animal model is attenuated by surgically induced endometriosis. This finding supports the idea that endometriosis might be associated with decreased bone mineral density.

Absorptiometry, Photon↗

PubMed2001

Composite tumor consisting of dermatofibrosarcoma protuberans and giant cell fibroblastoma associated with intratumoral endometriosis. Report of a case.

We present a unique case of composite skin tumor of the vulva consisting of dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) with an intratumoral focus of endometriosis. A 31-year-old female with a 10-year-history of a recurring subcutaneous tumor in the vulvar area underwent excision of the seventh recurrence of the tumor. Microscopic examination revealed a composite fibrohistiocytic tumor consisting of DFSP and GCF. Additionally, a focus of endometriosis within the tumor tissue was found. Malignant transformation of extragonadal endometriosis has already been described; we present, however, the occurrence of a focus of endometriosis within the tissue of a hormonally independent soft tissue tumor. There is a possible link to the occurrence of cutaneous endometriosis at previous surgery sites and in the scars. The presence of endometriosis within the soft tissue tumor represents, to the best of our knowledge, a previously undescribed collision phenomenon.

Adult↗

PubMed2006

Analysis of two polymorphisms in the promoter region of matrix metalloproteinase 1 and 3 genes in women with endometriosis.

BACKGROUND: Matrix metalloproteinases are a family of proteolytic enzymes that can degrade extracellular matrix components and have been implicated in connective tissue remodeling associated with cancer invasion and metastasis. These proteins are also involved in the invasive events underlying endometriotic lesion formation and aggressive behavior. Given the established genetic background of endometriosis, the aim of this study was to examine the potential impact of two polymorphisms in the gene promoter region of two of these enzymes, matrix metalloproteinases 1 and 3, on predisposition and severity of the disease. METHODS: Genomic DNA was obtained from 56 Italian Caucasian women with a surgical diagnosis of endometriosis and a control group of 71 age-matched Caucasian healthy female blood donors. In control women, endometriosis was ruled out by evaluation of the medical history, gynecologic examinations, and ultrasound scanning. Two polymorphisms have been specifically investigated: 1. a single insertion polymorphism (2G) in the matrix metalloproteinase-1 promoter region known to elevate transcriptional level of matrix metalloproteinase-1; and 2. a single insertion/deletion polymorphism (5A/6A) located in the promoter of the matrix metalloproteinase-3 gene with functional significance in the regulation of its expression. Genotypes were determined by PCR amplification and sequence analysis. RESULTS: Allele and genotype frequencies of both polymorphisms did not significantly differ between endometriosis and control groups. Moreover, no significant difference for both polymorphisms was observed in relation to the clinical stage and recurrence status of the disease. CONCLUSIONS: This is the first study that has evaluated the possibility that gene variants of matrix metalloproteinases might be involved in the susceptibility to endometriosis. However, these results suggest that matrix metalloproteinases 1 and 3 promoter polymorphism do not constitute an important factor for the genetic predisposition to endometriosis and its invasive behavior in the Italian population.

Adult↗

PubMed2004

The impact of endometriosis upon quality of life: a qualitative analysis.

OBJECTIVE: to explore and describe the impact of endometriosis upon quality of life. SETTING: Nuffield Department of Obstetrics and Gynaecology, University of Oxford. DESIGN: qualitative study. SAMPLE: twenty-four women with a laparoscopic diagnosis of endometriosis. METHODS: face to face, individual, in-depth interviews. RESULTS: analysis of the data revealed 15 descriptive categories. Pain, physical functioning, role performance, social functioning, emotional well-being, relationship with the medical profession, treatment, sexual intercourse, energy and vitality, employment and infertility were found to be a particular concern for women with endometriosis. Physical appearance, lack of control and powerlessness, feelings of social isolation and concerns that their daughters might develop endometriosis were new areas found to be negatively affected by the condition. CONCLUSIONS: the impact of endometriosis-associated symptoms upon quality of life is multidimensional and more complex than just negatively affecting psychosocial parameters. Conducting in-depth interviews to explore the subjective experiences of patients with endometriosis enabled the diverse areas of quality of life to be identified. Adopting a qualitative methodology is essential for item generation on disease specific health status questionnaires.

Adult↗

PubMed2001

Current place of progestins in the treatment of endometriosis-related complaints.

Oral progestins have been used for the treatment of endometriosis and endometriosis-associated complaints for more than 40 years. The mechanism of action on the menstrual cycle is well understood; however, the mechanism of action on endometriosis is still a matter of debate. The different progestins are able to stop proliferation in endometriotic implants and to induce regressive change to certain degrees; they are not able to heal endometriosis because endometriosis is a chronic and recurrent disease. For this reason, no medical treatment can heal endometriosis and repeat medication is necessary in the medical management of this disease. Progestins--especially non-androgenic progestins--are well tolerated and have only few side-effects; they can be used repeatedly or continuously over a long period of time.

Cell Division↗

PubMed2006

Laparoscopic partial cystectomy in the management of bladder endometriosis: report of two cases.

Endometriosis is the proliferation of endometrial tissue outside the normal confines of the myometrium or uterine cavity. Endometriosis involving the urinary tract occurs in approximately 1% to 2% of cases. The bladder is affected in 80% of these patients. The diagnosis of vesical endometriosis is difficult, and it should be confirmed by cystoscopy with biopsy. Laparoscopic examination represents the gold standard for the diagnosis of pelvic endometriosis. Urinary bladder endometriosis may be treated surgically or medically with hormone-suppressive therapy. However, medical treatments usually are only palliative, and symptoms generally recur on discontinuation. We report our experience in two patients with vesical endometriosis who were managed successfully with cystoscopy-assisted laparoscopic partial cystectomy.

Adult↗

PubMed2006

Simultaneous laparoscopic treatment for rectosigmoid and ileal endometriosis.

Endometriosis is common in women of childbearing age, while severe intestinal endometriosis requiring bowel resection is relatively rare. Intestinal endometriosis has recently been managed laparoscopically. We report the case of a 38-year-old patient with rectosigmoid and ileal endometriosis who was successfully treated by laparoscopic bowel resections. The patient had first presented at age 34 years with a chief complaint of rectal bleeding and lower abdominal pain related to the menstrual cycle. She underwent laparoscopic surgery and was diagnosed with severe endometriosis involving the rectosigmoid colon. Although an additional laparoscopic surgery had been planned, she did not return to the hospital. When she was 38 years old, she presented again with the same symptoms. Magnetic resonance imaging revealed a low intensity mass between the uterus and the rectosigmoid colon. A barium enema showed a stenotic site in the rectosigmoid colon. After hormone therapy, she underwent laparoscopic surgery. The anterior wall of the rectosigmoid colon adhered firmly to the corpus of the uterus, and another stenotic site was identified at the terminal ileum. The rectosigmoid colon and ileum were partially resected under laparoscopy. The postoperative course was uneventful and she was freed of symptoms. Laparoscopic treatment for patients with severe endometriosis of the bowel has becomes feasible and safe.

Adult↗

PubMed2001

GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer.

It is likely that heritable genetic factors contribute to the development of endometriosis, which is a putative precursor of the endometrioid and clear cell histological subtypes of ovarian cancer. The phase II glutathione S-transferases (GSTs) are a family of enzymes responsible for metabolism of a broad range of xenobiotics and carcinogens. Allelic variants of GSTs that have impaired detoxification function may increase the rate of genetic damage and thereby increase the susceptibility to cancer. The null genetic polymorphism in the gene encoding the GST class mu (GSTM1) enzyme has been reported to be significantly elevated in endometriosis patients and may represent an endometriosis susceptibility allele. In this study the frequency of the GSTM1 null genotype was investigated in 84 cases of endometriosis, 293 cases of ovarian cancer and 219 controls. All cases and controls were derived from women resident in the south east of England. The frequency of the GSTM1 null allele was not over-represented in the endometriosis patients (47.6%) compared with the controls (48.9%) (P = 0.898). In the ovarian cancer group the GSTM1 null genotype was significantly elevated compared with controls (59.0 versus 48.9%, P = 0.025). When stratified according to histological subtype a significantly increased GSTM1 null genotype was only observed for the endometrioid (65.4%, P = 0.013) and the combined endometrioid/clear cell ovarian cancers (67.0%, P = 0.004). We conclude that the GSTM1 null allele is not an endometriosis susceptibility allele, however, it may predispose endometriotic lesions to malignant transformation to endometrioid and clear cell ovarian cancer.

Case-Control Studies↗

PubMed1998

Profile of endometriosis in the aging female rhesus monkey.

BACKGROUND: A retrospective analysis was conducted on necropsy records from a large rhesus monkey colony to evaluate the age-related prevalence of endometriosis. METHODS: A total of 314 records collected over a 15-year period were analyzed, yielding 66 monkeys with histologically verified endometriosis and 248 control subjects. RESULTS: The analyses demonstrated that the incidence of endometriosis increases progressively across the life span, ultimately impacting 21-45% of aged monkeys over 20 years of age. CONCLUSIONS: Because mild disease is often not diagnosed premortem, the endocrine and immune sequelae of endometriosis may be a potential confound in even nonreproductive research with aging primates. Prior research-related events influence the occurrence and severity of endometriosis in these long-lived animals, and specifically could have contributed to the high prevalence of endometriosis in this particular monkey colony.

Abdomen↗