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Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract.

OBJECTIVE: To compare the expression of genes playing a decisive role during the embryonic development of the female genital tract (WNT4, WNT5A, WNT7A, PAX8) in the peritoneum of patients with endometriosis and control patients. DESIGN: Experimental study using real-time polymerase chain reaction and in situ hybridization. SETTING: University-based laboratory. PATIENT(S): Patients with and without endometriosis undergoing surgery for benign indications. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of samples positive for gene expression by using real-time polymerase chain reaction, as well as relative expression values compared with housekeeping genes. Confirmation of results by in situ hybridization. RESULT(S): Expression of WNT7A and PAX8 was found in the normal peritoneum in approximately half of the patients with endometriosis in contrast to the controls. In patients with endometriosis WNT7A and PAX8 in histologically normal peritoneum (with no evidence of endometriosis, endosalpingiosis, or other changes) were confirmed by in situ hybridization. CONCLUSION(S): The expression of these genes in the normal peritoneum suggests that endometriosis can arise through metaplasia and can in the process make use of the developmental steps involved in the embryonic development of the female genital tract.

Endometriosis↗

Fractalkine in the peritoneal fluid of women with endometriosis.

OBJECTIVE: The objective of this study was to evaluate the presence of fractalkine in the ascites and the association between fractalkine levels in the ascites and endometriosis. METHODS: Peritoneal fluids and peripheral blood samples were obtained from patients undergoing laparoscopy for infertility work-up or laparoscopic cystectomy. Three samples of peritoneum were obtained from patients undergoing hysterectomy. Western blotting, RT-PCR and immunohistochemistry were performed. RESULTS: Fractalkine protein was detected in the ascites. Positive staining was confirmed in peritoneal surface cells and perivascular cells of the peritoneum. CX3CR1 positive cells were present in the cells in the peritoneal fluid. The fractalkine concentrations in the ascites of patients with endometriosis were lower than those without endometriosis. There was no significant difference between serum fractalkine levels in patients with and without endometriosis. CONCLUSION: The decreased level of fractalkine found in the peritoneal fluid of patients with endometriosis may contribute to the pathogenesis of endometriosis.

Adult↗

Endometriosis: what is the risk of hospital admission, readmission, and major surgical intervention?

STUDY OBJECTIVE: To describe trends in hospital utilization and surgical rates for endometriosis and to estimate the probability of hospital readmission over 4 years among women with early-stage disease. DESIGN: Population-based, retrospective cross-sectional and longitudinal analysis of 53,385 hospital admissions for same-day surgery or inpatient treatment of endometriosis from fiscal years 1994/95 through 2001/02 (Canadian Task Force classification III). SETTING: All hospital discharge records that listed endometriosis as the most-responsible diagnosis in the province of Ontario, Canada, from fiscal years 1994-1995 through 2001-2002. PATIENTS: Ontario female patients 15 years of age or older admitted to the hospital for treatment of endometriosis. INTERVENTIONS: Surgical treatments were classified as minor, intermediate, or major depending on the extent of the surgery. MEASUREMENTS AND MAIN RESULTS: Age-standardized annual discharge rates were calculated and trends in surgical treatment described. The records of 7993 women who received minor or intermediate surgery on their index hospital visit were linked, and the likelihood and predictors of readmission were calculated using survival analysis and logistic regression. During the observation period, the standardized discharge rates fell significantly from 172.9 per 100,000 women aged 15 to 70 to 137.1 per 100,000 (p<.05). Age-specific rates were highest for women aged 15 to 39 (approximately 200 per 100,000). The proportion of hospitalizations involving minor surgeries dropped (from 27% to 17%), and the proportion involving intermediate surgeries increased (from 40% to 53%). The likelihood of hospital readmission within 4 years for additional surgical treatment was 27% and of having a hysterectomy was 12%. CONCLUSION: Fewer women are being hospitalized for minor surgical procedures for endometriosis with hospital-based care being reserved for more extensive procedures. Nonetheless, about a quarter of women hospitalized for initial surgical treatment for endometriosis will undergo additional surgical treatment within 4 years, and one in 10 will have a hysterectomy.

Adolescent↗

Villar's nodule: a case report and systematic literature review of endometriosis externa of the umbilicus.

We report a case of umbilical endometriosis externa and systematically review the literature regarding this finding. In our case report, a 47-year-old woman with cyclic umbilical bleeding, pelvic pain, and no previous umbilical surgery developed a spontaneous umbilical endometrioma, cured by surgical resection and bilateral salpingo-oophorectomy. In our review, 122 patients with documented umbilical endometriomas from 1966 to the present and 109 cases reported before 1953 were analyzed. Procedures used for diagnosis and/or therapeutic intervention included umbilical biopsy or resection, abdominal wall repair, diagnostic and/or operative laparoscopy, adhesiolysis, hysterectomy, and bilateral salpingo-oophorectomy. Variables included patient age; race; medical and surgical history; past use of oral contraceptives; history of umbilical pain, bleeding, or swelling; duration of signs and symptoms; size and color of the lesion; diagnostic evaluations; and medical or surgical management. Mean age of the study population was 37.7 +/- 0.98 years. Up to 40% of patients with extrapelvic endometriosis present with umbilical endometriomas, with symptoms occurring an average of 17.8 +/- 3.9 months before presentation. Lesions averaged 2.3 +/- 0.2 cm in diameter; were predominantly brown (19.1%), blue (13.2%), or purple (10.3%); and patients frequently had with pain (77.93%), cyclical bleeding (47.1%), and swelling (88.2%). Most patients had no history of endometriosis (73.1%), and laparoscopic, umbilical trocar-related seeding was identified in only 5 patients. Three patients received medical management, and surgical management was invariably curative, though 1 patient required repeat surgical therapy. Umbilical endometriosis is a common manifestation of external endometriosis, representing primary or secondary endometriosis, with a typical presentation that has little variation. Laparoscopic endometrioid tissue excision can result in iatrogenic seeding to the umbilicus. Historical and physical findings are pathognomonic, thus justifying a formal name--Villar's nodule, after the initial reporting physician. Surgical intervention is recommended, but medical therapy may result in long-term symptom control with minimal malignancy risk.

Endometriosis↗

Concentrations of alpha-fetoprotein, insulin-like growth factor binding protein-3, c-erbB-2, and epidermal growth factor in serum of patients with endometriosis.

OBJECTIVE: Endometriosis, although it is a benign disorder, shares many similarities with cancer. There is increasing levels of evidence suggesting that some circulating factors involved in gynecologic cancers, such as alpha-fetoprotein (AFP), insulin-like growth factor binding protein-3 (IGFBP-3), c-erbB-2 (HER-2/neu), and epidermal growth factor (EGF), could also play a role in endometriosis. Hence, the present study was aimed at evaluating whether the levels of these molecules are modulated in the serum of patients with endometriosis. METHODS: Levels of AFP, IGFBP-3, c-erbB-2, and EGF were determined by enzyme-linked immunosorbent assay in serum from 36 subjects with surgically confirmed endometriosis and 36 controls with no surgical evidence of the disease. In addition, information such as demographic characteristics, personal habits, menstrual characteristics, and clinical profile was collected from each participating subject. RESULTS: No significant difference was found between serum levels of AFP, IGFBP-3, c-erbB-2, and EGF in patients with endometriosis and controls, even when we adjusted for potential confounders and took into account the menstrual cycle. Moreover, no correlation was observed between the serum concentrations of these molecules and the stage of the disease. However, a correlation was detected between soluble levels of IGFBP-3 and presence of uterine leiomyoma. CONCLUSION: Although AFP, IGFBP-3, c-erbB-2, and EGF are not altered in the circulation of patients with endometriosis, their involvement in the development of endometriotic lesions cannot be excluded.

Adolescent↗

Association study of endometriosis and intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in a Japanese population.

OBJECTIVE: Endometriosis is an immune-related, chronic inflammatory disease with polygenic predisposition. Cell adhesion molecules are expressed in endometriotic lesions, and in cells and tissues that are involved in the development and progression of the disease. In this study, we investigated the possible association between endometriosis and the G241R and K469E polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene in a Japanese population. METHODS: We compared the distribution of the G241R and K469E polymorphisms in the ICAM-1 gene in 126 endometriosis patients and 172 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in a Japanese population. RESULTS: There were no significant differences between the cases and controls in the allele frequencies or genotype distributions of either the G241R or K469E polymorphisms in the ICAM-1 gene. The endometriosis patients were divided into a subgroup of women with severe disease only. However, no significant differences were observed in the allele frequencies and genotype distributions of the ICAM-1 K469E polymorphisms between this subgroup and the controls. In contrast, only one in 169 controls was heterozygous (G/A genotype), and the A allele in the G241R polymorphism was not found in any of the 126 endometriosis patients. CONCLUSION: Our findings suggest that the G241R and K469E polymorphisms in the ICAM-1 gene are unlikely to be associated with an increased risk of endometriosis in the Japanese population.

Case-Control Studies↗

The depolarized expression of the alpha-6 integrin subunit in the endometria of women with endometriosis.

OBJECTIVE: The current study sought to compare the endometrial localization of the integrin subunit alpha-6 in women with endometriosis and women without the disease. Alpha-6 integrins have an important function, not only in the attachment of cells to the extracellular matrix and laminin, but they also serve as inductors of cell migration and invasion, depending on their pattern of expression in the cell membrane. METHODS: The endometriosis group consisted of 32 women with a confirmed diagnosis of endometriosis by laparoscopy or laparotomy. The control group consisted of 20 women not having endometriosis or any other gynecologic disease at laparoscopy. Endometria were obtained by biopsy. Immunohistochemical techniques were used to assess alpha-6 localization. In each section, the percentage of positive cells and the localization of expression were evaluated. RESULTS: All glandular cells expressed alpha-6 in all of the samples but presented two different patterns, either only in the basal side of the cells (polarized) or also in other sides of the cells (depolarized). The percentage of samples showing depolarized expression was significantly higher in the endometriosis group (66.6% vs 15.8%, chi2 =12.09, P = .001). CONCLUSIONS: The endometria of women with endometriosis more frequently show a depolarized expression of integrin subunit alpha-6, a characteristic usually found in highly proliferating cells with migrating and invasive abilities.

Adult↗

Impaired NK-cell-mediated cytotoxic activity and cytokine production in patients with endometriosis: a possible role for PCBs and DDE.

Endometriosis is a gynaecological disorder characterized by the presence and growth of endometrial tissue in ectopic sites. In this study we examined the immunological functions of patients with endometriosis and serum level of PCBs and p,p'-DDE to verify the impact of these environmental contaminants on the dysregulation of immune functions. We found that proliferative responses and immunoglobulin production were not dysregulated in patients with endometriosis while NK cell activity was significantly down-regulated in these patients. Moreover, a significant down-regulation of IL-1beta and IL-12 production was found in patients with respect to controls. Serum levels of PCBs and p,p'-DDE were found to be significantly higher in women with endometriosis than in the control group, with respect to the sum of the congeners most prominent in human tissues. In particular, total PCBs concentration in patients with endometriosis and controls was respectively 330 and 160 ng/g fat with respect to the most abundant congeners, while p,p'-DDE concentration was of 770 and 310 ng/g fat. Moreover, we found that normal human PBMC pulsed with PCBs, p,p'-DDE and their combination showed a significant down-regulation of NK cell cytotoxic activity and IL-1beta and IL-12 production. These findings suggest that changes in specific immune parameters correlate with elevated serum PCBs and DDE levels and endometriosis.

Adolescent↗

Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility.

OBJECTIVE: We attempted to clarify the relationship between luteinized unruptured follicle, which occurs in the early stages of endometriosis, and unexplained infertility. STUDY DESIGN: Seventy patients who had unexplained infertility were reviewed. RESULTS: Laparoscopic examination showed that 47 patients (67%) had endometriosis; of these, 40 (85%) had minimal or mild disease. The incidence of luteinized unruptured follicle was higher (p < 0.05) in patients who had endometriosis (35%/patient and 25%/cycle) compared with patients who did not have endometriosis (11%/patient and 7%/cycle). Degenerated oocyte cumuli were collected in 6 (43%) of 14 luteinized unruptured follicles diagnosed by transvaginal ultrasound. CONCLUSIONS: These results show that luteinized unruptured follicle is common in patients who have mild or minimal endometriosis and that it may be one of the causes of endometriosis-associated infertility. Transvaginal ultrasound-guided follicular puncture of luteinized unruptured follicle during the mid luteal phase may be useful in establishing a definitive diagnosis of luteinized unruptured follicle.

Corpus Luteum↗

The impact of endometriosis on the reproductive outcome of infertile patients.

OBJECTIVE: We examined whether the presence and severity of endometriosis affect the reproductive outcome of infertile patients. STUDY DESIGN: The conception rates of 2080 infertile women, 1263 who had endometriosis and 817 who did not have endometriosis, were analyzed retrospectively by means of the chi 2 test. Depending on the stage of the disease patients who had endometriosis-associated infertility underwent expectant management, danazol therapy, or minor or major conservative surgery. The patients who failed to conceive after these conventional treatments were enrolled in the in vitro fertilization-embryo transfer program. RESULTS: The conception rates were virtually identical regardless of the presence or absence of endometriosis (30.7% vs 30.0%). The outcome of in vitro fertilization-embryo transfer was not affected either by the presence or the severity of the disease. CONCLUSION: Endometriosis had no impact on the reproductive outcome of infertile patients in this series unless the anatomy of the pelvic organs was heavily distorted, which can occur in the advanced stages of the disease.

Adult↗

Estrogen and progestin receptors in endometriosis lesions: comparison with endometrial tissue.

Cytosol estrogen (ER) and progestin (PR) receptors were quantified in 47 endometriosis lesions from 41 patients and compared with receptor measurements in the endometrial tissue of nine of these patients. Half of the specimens of endometriosis tissue contained PR only, in concentrations that were significantly lower than in the endometrium. Only 30% of the specimens of endometriosis tissue contained the two receptors simultaneously, and levels of ER were very low compared with those in the endometrium. Levels of PR in the specimens of endometriosis tissue were highest at the periovulatory period, whereas concentrations of ER tended to be highest at the beginning and close to the end of the cycle. These results suggest that regulation of these receptors is dissimilar in endometriosis lesions and endometrium. It remains to be seen whether differences in receptor distribution in the lesions of individual patients could explain differences in the course of this disease, and have therapeutic implications. The presence of PR in the majority of the endometriosis lesions is in accord with the favorable therapeutic response often obtained with progestin treatment of this disease.

Adult↗

Comparison of different modalities of treatment for minimal and mild endometriosis.

This is a retrospective study designed to compare the results of treatment of minimal and mild types of endometriosis with danazol alone, operative laparoscopy and danazol combined, and operative laparoscopy alone. The population consisted of 112 patients with minimal endometriosis and 126 patients with the mild type. Pregnancy rate and endometriosis resolution were lowest in patients who were treated with danazol alone and highest in patients treated with operative laparoscopy alone. It is concluded that in an infertile population with minimal to mild endometriosis danazol alone appears ineffective in improving the pregnancy rate or in achieving complete resolution of endometriosis. Laparoscopic surgery for the treatment of minimal to mild endometriosis seems to be a promising method of treatment.

Combined Modality Therapy↗

Decrease in interferon gamma production and impairment of T-lymphocyte proliferation in peritoneal fluid of women with endometriosis.

OBJECTIVE: Our purpose was to verify regional immune modulations and to test the effect of gonadotropin-releasing hormone agonist in women with endometriosis. STUDY DESIGN: Concentrations of peritoneal cytokines, including interleukin-1 beta, interleukin-2, soluble interleukin-2 receptor, interleukin-6, granulocyte-monocyte colony-stimulating factor, interferon gamma, and tumor necrosis factor-alpha were compared in women with and without endometriosis. Peritoneal cytokine and interleukin-2 production were examined by adding various mitogens to peritoneal fluid mononuclear cells of women with advanced endometriosis before and after gonadotropin-releasing hormone agonist treatment. RESULTS: A significant increase in peritoneal interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha and a decrease in interferon gamma were noted in women with endometriosis. After gonadotropin-releasing hormone agonist treatment interleukin-6 decreased and interferon gamma increased. A significant impairment of interleukin-2 production of peritoneal fluid mononuclear cells by phytohemagglutinin and pokeweed mitogen stimulation was demonstrated in endometriosis, and production could be restored after gonadotropin-releasing hormone agonist treatment. CONCLUSION: These results indicate that regional immunologic dysfunction might be invoked in the disease process of endometriosis.

Ascitic Fluid↗

Increased monocyte chemotactic protein-1 level and activity in the peripheral blood of women with endometriosis. Le Groupe d'Investigation en Gynécologie.

OBJECTIVE: Our purpose was to evaluate monocyte chemotactic protein-1 in the peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty-seven patients with endometriosis at laparoscopy done for infertility and pelvic pain were compared with 44 fertile women with no evidence of endometriosis at tubal ligation by laparoscopy. Monocyte chemotactic protein-1 concentration in the plasma was determined by enzyme-linked immunosorbent assay and its biologic activity was evaluated by measuring monocyte chemotaxis with use of a human histiocytic cell line (U937). RESULTS: Monocyte chemotactic protein-1 concentrations (median and range of values) found in the plasma were higher in patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0 to 355 pg/ml). This elevation was significant only in the minimal stage of endometriosis (revised American Fertility Society stage I). However, increased chemotactic activity (mean number of migrating cells/mm2 +/- SEM) was found in the stages I (1240 +/- 141), II (519 +/- 30), and III-IV (523 +/- 23) of the disease compared with normal controls (205 +/- 20). A total of 35% to 44% of this activity was inhibited in the presence of an antibody specific to monocyte chemotactic protein-1. CONCLUSION: Endometriosis is associated with increased level and activity of monocyte chemotactic protein-1 in the peripheral blood. The elevation and activation of this cytokine could play a relevant role in the immunoinflammatory process associated with the disease.

Adult↗

Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis.

OBJECTIVE: The levels of interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-10, and granulocyte-macrophage colony-stimulating factor were measured in the peritoneal fluid of 15 patients with endometriosis to characterize the type of immune response that occurs at the site of endometriosis. STUDY DESIGN: Cytokine levels in peritoneal fluid obtained during laparoscopy from 15 patients and 12 controls undergoing tubal ligation were determined by enzyme-linked immunosorbent assay. RESULTS: The mean levels of interleukin-6 in patients with endometriosis and controls were 797 +/- 407 pg/ml and 133 +/- 38 pg/ml, respectively (p < 0.02). Similarly, the mean concentration of interleukin-10 in peritoneal fluids of patients with endometriosis was significantly higher than that of controls (241 +/- 38 vs 128 +/- 21, p < 0.05). The levels of interleukin-2, interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly different between the two study groups. CONCLUSIONS: The levels of interleukin-6 and interleukin-10 are increased in the peritoneal fluids of patients with endometriosis, suggesting enhanced macrophage activity in these patients. Increased interleukin-6 and interleukin-10 production may partially contribute to the disturbed immune regulation observed in patients with endometriosis.

Adult↗

Extrapelvic endometriosis: diagnosis and treatment.

BACKGROUND: Young women with nondescript abdominal pain can be difficult to diagnose. Although extrapelvic endometriosis is infrequent, we have treated 7 patients over the past 3 years with endometriosis in the abdominal wall, inguinal canal, or surgical incisions as the etiology of their symptoms. PATIENTS AND METHODS: We reviewed the medical records of patients whose final pathology report confirmed a diagnosis of extrapelvic endometriosis. Seven women who were treated at the University of Rochester Strong Memorial Hospital from May 1, 1991 through April 30, 1994 were identified. RESULTS: All patients were premenopausal with no history of pelvic endometriosis. In 4 patients, symptoms were cyclical. Surgical excision was initially curative in 5 patients. Two women required reexcision. The diagnosis of endometriosis was established at exploration by gross appearance and by frozen section. CONCLUSIONS: Endometriosis should be included in the differential diagnosis of a symptomatic mass in a celiotomy scar, the abdominal wall, or the inguinal canal. Principles of management include obtaining an accurate diagnosis and performing an adequate excision to prevent recurrence.

Abdominal Pain↗

[Symptomatic bladder or ureteral endometriosis: report of 8 cases and review of the literature].

OBJECTIVES: The aim of this study was to determine the symptoms of bladder and ureteral endometriosis and to review the treatment approaches. MATERIALS AND METHODS: We conducted a retrospective studyover the period November 1989-July 2000. We reviewed the medical data of all women with bladder or utereral endometriosis who underwent a major surgery (ureteral reimplementation on psoas bladder, partial resection of the ureter, partial cystectomy). RESULTS: Eight women met the defined selection criterion, three with bladder injuryand five with ureteral injury. The only adverse postoperative complication was a passive ureteral reflux following ureteral reimplementation on psoas bladder. No recurrence on the urinary tract were reported. CONCLUSION: Surgical treatment is indicated for patient suffering from symptomatic bladder or ureteral endometriosis. Isolated bladder injuries due to endometriosis are mostly treated by laparoscopic surgery. Ureteral endometriosis may deteriorate the renal function. The initial step of the treatment may include an uterolysis by coelioscopy or an ureteral dilatation by ureteroscopy together with a medical treatment. The renal function must be closely monitored. In case of persistent or recurrent endometriosis, an ureteral resection would be justified.

Adult↗

Deep endometriosis conundrum: evidence in favor of a peritoneal origin.

OBJECTIVE: To determine whether the depth and volume of the pouch of Douglas differs in patients with endometriosis with and without deep lesions and to compare them with subjects with a healthy pelvis or with diseases other than endometriosis. DESIGN: Prospective, comparative study. SETTING: Tertiary care and referral center for patients with endometriosis. PATIENT(S): Women undergoing laparoscopy for infertility, pelvic pain, or adnexal anomalies (deep endometriotic rectovaginal lesions in 16 cases, endometriosis without deep lesions in 127 cases, miscellaneous anomalies in 35 cases, and normal pelvis in 26 cases). INTERVENTION(S): Douglas pouch depth measurement from the upper border of uterosacral ligaments to its base with a calibrated probe and volume assessment by a fluid-filling technique. MAIN OUTCOME MEASURE(S): Douglas pouch depth and volume. RESULT(S): Mean (+/-SD) Douglas pouch depth and volume measurements were 3.6 +/- 1.6 cm and 41.6 +/- 19.3 mL in women with deep endometriosis, 5.3 +/- 0.8 cm and 67.2 +/- 18.1 mL in those with peritoneal and ovarian lesions only, 5.2 +/- 0.9 cm and 67.6 +/- 12.6 mL in those with miscellaneous conditions, and 5.5 +/- 0.8 cm and 65.8 +/- 10.9 mL in those with normal pelvis. CONCLUSION(S): Reduced Douglas pouch depth and volume in women with deep endometriosis suggest that such lesions develop not in the rectovaginal septum but intraperitoneally and that burial by anterior rectal wall adhesions creates a false bottom, giving an erroneous impression of extraperitoneal origin.

Adult↗