Endoscopic diagnosis of colonic endometriosis.

Involvement of the colon or rectum with endometriosis is uncommon but may be a cause of gastrointestinal symptoms such as diarrhea, pain, and bleeding. To determine whether endoscopy has a role in evaluating endometriosis of the colon, we reviewed all cases of endometriosis undergoing colonic resection from 1984 to 1989. There were nine patients, six of whom had intermittent hematochezia. All had lesions detected at endoscopy described as a polyp, mass, or stricture. Five of the six patients with symptoms of hematochezia had mucosal involvement in the resected specimen. Four of these five had a visible lesion at endoscopy with endometriosis on biopsy. The three patients without hematochezia had no mucosal endometriosis in the resected colonic specimen or endometrial tissue on biopsy. In patients with colonic endometriosis and hematochezia, endoscopy and biopsy can confirm the diagnosis of colonic endometriosis.     

Expression of vascular endothelial growth factor (VEGF) and its soluble receptor-1 in endometriosis

The aim of this study is to evaluate the expression of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) in peritoneal fluid (PF), peritoneal endometriotic lesions and eutopic endometrial tissues of patients with endometriosis. Peritoneal fluid, peritoneal endometriotic lesions and eutopic endometrial samples from patients with endometriosis, and peritoneal fluid, peritoneal tissue and endometrial samples from patients without endometriosis were obtained during an operative laparoscopy. The mean PF concentrations of VEGF and sFlt-1 were significantly higher in patients with endometriosis than in the controls. In the peritoneal tissue, the expressions of VEGF and sFlt-1 were significantly higher, where the expression of sFlt-1 in endometrium was significantly lower in patients with endometriosis. These findings indicate that not only abnormal expressions of angiogenic factors, but also aberrant expressions of antiangiogenic factors in the peritoneal and endometrial environment seem to be involved in the pathogenesis of endometriosis.     

Pulmonary endometriosis

Pulmonary endometriosis is manifested as either asymptomatic pulmonary nodules or as pneumothorax, hemothorax, or hemoptysis during menses. We review 84 cases of pulmonary endometriosis in the English literature and report 3 additional patients. One of our patients is the first reported to have hemoneumothorax. Catamenial pneumothorax usually involved the right chest, and occurred in young nulliparous women without pelvic endometrosis. Pleuroscopy, laparoscopy with pneumoperitoneum, and thoracotomy produced a tissue diagnosis infrequently. Hormonal suppression of ovulation and pleurodesis usually corrected this disorder. Catamenial hemothorax only affected the right chest, but occurred in older multiparous women with pelvic endometriosis. While thoracotomy or laparotomy produced a tissue diagnosis, these procedures were not curative. In contrast, our patient with this disorder was treated successfully with pleurectomy. Catamenial hemoptysis occurred in multiparous women without pelvic endometriosis. Bronchoscopy localized bleeding but never produced a tissue diagnosis. Thoracotomy produced endometrial tissue. Endometrial pulmonary nodules require a diagnosis but do not otherwise produce problems.     

子宫内膜异位症患者异位、在位子宫内膜组织中VEGF、sflt-1 mRNA表达变化

目的观察子宫内膜异位症患者异位、在位子宫内膜组织中VEGF、sflt-1 mRNA表达变化。方法收集46例子宫内膜异位症患者的异位子宫内膜组织46份为异位组,在位子宫内膜组织32份为在位组,另收集30例非子宫内膜异位症患者子宫内膜组织为对照组。采用实时荧光定量PCR法检测各组VEGF mRNA、sFlt-1 mRNA,采用比较阈值法（2-△△Ct法）计算VEGF mRNA、sflt-1 mRNA相对表达量。结果在位组VEGF mRNA表达量明显高于对照组和异位组（P均〈0.05）,对照组VEGFmRNA表达量高于异位组（P〈0.01）;在位组内膜VEGF活性指数高于异位组和对照组（P〈0.05）,异位组VEGF活性指数高于对照组,但差异无统计学意义;对照组内膜sflt-1mRNA表达量高于在位组和异位组（P〈0.05）,在位组sflt-1mRNA表达量高于异位组（P〈0.05）。结论子宫内膜异位症患者异位、在位子宫内膜组织中VEGF、sflt-1 mRNA表达异常。sflt-1可能参与了子宫内膜异位症的发病过程。     

Catamenial pneumothorax: a prospective study

OBJECTIVES: To evaluate the incidence of catamenial pneumothorax (CP) among women who have been referred for the surgical treatment of spontaneous pneumothorax (SP) and to study its pathogenic mechanisms. DESIGN: A prospective study of women of reproductive age who have been referred to our center for the surgical treatment of SP. Patients with pneumothorax secondary to a known lung disease were excluded. SETTING: A university hospital. METHODS: At the preoperative evaluation, special attention was given to the investigation of a possible temporal relationship between pneumothorax and menses. Video-assisted thoracoscopy constituted the operative technique of choice. The lung was inspected to identify blebs or bullae and the origin of possible air leaks. Signs of thoracic endometriosis were also carefully searched for. The diaphragm was systematically inspected to search for holes and/or endometrial implants. When limited diaphragmatic abnormalities were found, a partial diaphragmatic resection was carried out using an endoscopic stapler. In case of lesions that were not accessible by a purely endoscopic approach, a utility minithoracotomy was used. RESULTS: In an 18-month period, 32 women with SP were referred for surgery. In eight cases, the catamenial character of the pneumothorax was recognized by clinical history. In all these patients, the following diaphragmatic abnormalities were found at surgery: holes (one patient); endometrial implants (three patients); and both (four patients). Visceral pleural endometriosis was found in one patient. During pathologic examination, diaphragmatic endometriosis was confirmed in seven of the eight cases. In one patient, it was associated with pulmonary and pleural endometriosis. In only one patient (with multiple diaphragmatic holes and a pulmonary nodular brown lesion), endometriosis could not be confirmed at histology, but signs of parenchymal focal hemorrhages were found. CONCLUSIONS: Our experience shows that (1) CP is more frequent than expected and (2) diaphragmatic abnormalities seem to play a fundamental role in its pathogenesis.     

Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget

CONTEXT: Endometriosis, the growth of endometrial tissue outside the uterus, is principally an estrogen-dependent disease. In contrast, exposure to progesterone during pregnancy or therapeutically has been shown to provide benefit to some women with this disease. However, recent research suggests that the presence of endometriosis impairs the capacity of the eutopic endometrium to respond to endogenous progesterone. OBJECTIVE: Reduced progesterone responsiveness results in an elevated endometrial expression of matrix metalloproteinases (MMPs) during the secretory phase of the menstrual cycle in women with endometriosis. Although cyclic MMP expression is critical for endometrial growth and remodeling, the failure of progesterone to down-regulate MMPs may impair nidation and promote the invasive establishment of endometriosis. In the current study we examined the ability of a newly developed progesterone receptor (PR) agonist, tanaproget (TNPR), to down-regulate endometrial MMP expression in vitro and regress experimental endometriosis in vivo. SETTING: This study was performed at a university-based medical center. PARTICIPANTS: Asymptomatic volunteers and patients with endometriosis were studied. MAIN OUTCOME MEASURES: We examined the ability of TNPR to down-regulate endometrial MMP expression in vitro compared with that of natural progesterone and two currently marketed synthetic steroidal progestins. Using a human/mouse model of endometriosis, we also tested the in vivo ability of TNPR to regress ectopic lesions established by tissues with reduced progesterone sensitivity. RESULTS: TNPR effectively down-regulated MMP expression in vitro and induced significant reduction of lesions in mice with disease established by tissues from endometriosis patients. CONCLUSION: Given the positive preclinical pharmacological profile of TNPR that has recently been reported, additional development of this compound for the treatment of endometriosis is warranted.     

Catamenial hemoptysis from endobronchial endometriosis in a child with type 1 von Willebrand disease

Catamenial hemoptysis is a rare condition characterized by cyclic pulmonary hemorrhage, synchronous with menses and associated with the presence of intrapulmonary or endobronchial endometrial tissue. Because of the paucity of cases reported in the literature, information regarding the natural history is limited and also the optimal diagnostic workup and management of these patients are not well defined. In this report, we present a case of endobronchial endometriosis in a 12-year-old female diagnosed by bronchoscopy and immunocytochemical assay, associated with type 1 von Willebrand disease.     

Endometriosis,need for a multidisciplinary clinical setting: the internist’s point of view

Endometriosis is a common condition characterized by proliferation of endometrial tissue outside the uterus, both in the pelvis and in other extra-pelvic sites. The clinical picture of endometriosis is widely heterogeneous. A correct diagnostic work-up of these patients can sometimes be very difficult, since there are a number of gynecological, intestinal and systemic diseases mimicking endometriosis, as well as other conditions that could be associated with or are a consequence of this disorder. Therefore, multidisciplinary care should be encouraged to ensure correct evaluation and improve the management of these patients.     

Production and secretion of complement component 3 by endometriotic tissue

Many investigators have described a variety of immune phenomena associated with endometriosis. Among these are elevated titers of activated macrophages, monokines, and lymphokines in the peritoneal fluid of patients with endometriosis. In 1980, Weed and Arquembourg first described the deposition of complement component C3 in epithelial cells of endometrial glands in patients with endometriosis. In this study our objective was to examine the synthesis and secretion of proteins by endometriotic tissue. Tissues were incubated in Minimal Essential Medium without methionine containing 50 microCi/mL [35S]methionine for 12-16 h at 37 C in 5% CO2-95% air. Twenty thousand trichloroacetic acid-precipitable counts were placed on a 7.5% sodium dodecyl sulfate-polyacrylamide gel, and the radiolabeled proteins were detected by fluorography. We examined the radiolabeled secretory proteins obtained from 17 endometriotic implants and/or endometrioma cyst walls as well as 8 control tissues. A 180 kDa protein was produced in much greater quantities by endometriotic tissue than by control tissues. In the presence of reducing agent this protein dissociated into 113- and 69-kDa subunits. To identify and quantitate this protein we performed immunoprecipitations on the incubated medium using antihuman C3 immunoglobulin G. Up to 16% of the precipitable counts were recovered with this antibody from endometriotic tissue, while a maximum of only 4.6% was recovered from control tissue. In addition, we isolated and incubated the epithelial glandular cells, stromal cells, and remaining cells from two endometriomas. The great majority of the newly synthesized and secreted C3 was found in the glandular epithelial cell incubation. Up to 60% of the total precipitable counts were recovered from the glandular cells using this antibody. Only one protein was immunoprecipitated. The immunoprecipitated protein had a mol wt of 180 kDa under nonreducing conditions and dissociated into two subunits of 113 and 69 kDa in the presence of dithiothreitol. We conclude that the glandular epithelial cells found in endometriotic implants produce and secrete complement component, C3 which could be responsible for many of the immunological phenomena now well described in endometriosis.     

Down-regulation of interleukin-1 receptor type 1 expression causes the dysregulated expression of CXC chemokines in endometriotic stromal cells: a possible mechanism for the altered immunological functions in endometriosis

To evaluate the involvement of chemokines in the pathogenesis of endometriosis, we investigated the expression of CXC chemokines in cultured ovarian endometriotic cyst stromal cells (ECSC), endometrial stromal cells with endometriosis (ESCwE), and normal endometrial stromal cells (NESC). Using ELISA, TNF-alpha significantly enhanced the production of IL-8, growth-related oncogene alpha, and epithelial neutrophil-activating peptide-78 in all cases of ECSC (n = 10), ESCwE (n = 6), and, NESC (n = 10). IL-1beta did not affect the production of these chemokines in eight of 10 cases of ECSC. In contrast, IL-1beta significantly enhanced the expression of these chemokines in all cases of ESCwE (n = 6) and NESC (n = 10). Western blot analysis revealed down-regulation of expression of IL-1 receptor type 1 (IL-1-R1) in all cases of ECSC with low response to IL-1beta (n = 8). In contrast, significant IL-1-R1 expression was detected in all cases of NESC. Although IL-1-R1 expression was detected in all cases of ESCwE (n = 6), its expression in ESCwE tended to decrease compared with that in NESC. Moreover, phosphorylation of inhibitor kappaB-alpha was detected in all cases of ESCwE and NESC after stimulation with IL-1beta, but not in ECSC with low response to IL-1beta (n = 8). In contrast, significant IL-1-R2 expression was detected in all cases of ECSC, ESCwE, and NESC. The present findings suggest that the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in endometriosis. The alteration of the CXC chemokines expression may be important for elucidation of the pathogenesis of endometriosis.     

线阵超声内镜对直肠子宫内膜异位症的诊断价值

目的:探讨线阵超声内镜对直肠子宫内膜异位症(rectal endometriosis,RE)的诊断价值.方法:对20例子宫内膜异位症患者于外科手术前行线阵超声内镜检查直肠,超声扫描频率为7.5MHz,根据直肠壁内有无边界不规则的低回声结节或团块判断直肠是否受累,并将超声内镜检查结果与手术中所见及术后病理进行比较.结果:20例患者中有12例经线阵超声内镜检查发现直肠壁内有异位子宫内膜病灶,其余8例患者的直肠壁正常.超声内镜诊断为RE的12例患者术中均见盆腔异位子宫内膜病灶与肠壁粘连紧密,手术切除的直肠病灶送检均见子宫内膜组织.超声内镜下未见直肠受累的8例患者盆腔子宫内膜异位病灶与肠壁无粘连或轻度粘连,易分离,分离缘组织送检未见子宫内膜组织.线阵超声内镜检查结果与手术中所见及术后病理完全一致.结论:线阵超声内镜检查是诊断RE的可靠方法,可对子宫内膜异位症患者是否伴有直肠受累做出准确的术前评估.     

Expression of scavenger receptor class B1 in endometrium and endometriosis

Endometriosis is characterized by the presence of endometrial glands and stroma within the peritoneum and other extrauterine sites. The presence of aromatase, a key enzyme in the biosynthesis of estradiol, has been demonstrated in eutopic endometrial samples of women with moderate to severe endometriosis, but not in those of disease-free women. Animal studies have shown that high density lipoprotein provides precursor cholesterol pool for steroidogenesis. Scavenger receptor class B1, a 82-kDa cell surface protein, is involved in the binding of high density lipoprotein to target cells and promotes cholesteryl ester uptake. In this study we detected the presence of scavenger receptor class B1 in eutopic and ectopic endometrium. There was more scavenger receptor class B1 protein associated with endometriosis compared with matched endometrium. Two bands (82 and 45 kDa) were detected in the endometrium and endometriosis samples. Glycanase treatment indicated that the 45-kDa protein might be a nonglycosylated form of scavenger receptor class B1. Immunostaining of fixed tissues detected scavenger receptor class B1 in glandular epithelium of both tissues. Scavenger receptor class B1 and aromatase mRNA were increased in endometriosis tissues. Scavenger receptor class B1 expression in the endometrium and endometriosis supports a role for this receptor in the uptake of high density lipoprotein cholesterol, possibly supporting in situ estrogen production, which is detrimental in the progression of endometriosis.     

Hepatocyte growth factor/Met system promotes endometrial and endometriotic stromal cell invasion via autocrine and paracrine pathways

Endometrial stromal cells reportedly have a role in the initial invasion of endometrial tissue into the peritoneum. Hepatocyte growth factor (HGF), which is a ligand for the c-met protooncogene product (Met), stimulates proliferation and invasion of a large number of cells. In this study we investigated the role of the HGF/Met system in the pathogenesis of endometriosis. HGF concentrations in the peritoneal fluid of patients with endometriosis were significantly higher than in those without endometriosis and correlated positively with revised American Society of Reproductive Medicine scores. We showed that the peritoneum and endometriotic stromal cells may be major sources of HGF in peritoneal fluid. Endometrial and endometriotic stromal cells expressed the Met receptor, which was activated by endogenous and exogenous HGF. HGF enhanced stromal cell proliferation and invasion. We also demonstrated that the HGF-stimulated stromal cell invasion was due in part to the induction of urokinase-type plasminogen activator, a member of the extracellular proteolysis system. In conclusion, the HGF/Met system is involved in the pathogenesis of endometriosis by promoting stromal cell proliferation and invasion of shed endometria and endometrial lesions via autocrine and paracrine pathways.     

The expression of human chorionic gonadotropin/human luteinizing hormone receptors in ectopic human endometrial implants.

Our laboratory previously demonstrated that normal human endometrium contains hCG/human LH receptors. Since ectopic endometrial implants in endometriosis arise directly at least in part from uterine endometrium, we investigated whether the implants continue the expression of these receptors. The presence of hCG/LH receptor mRNA and/or immunoreactive receptor protein in ectopic endometrial implants on pelvic peritoneum, uterine endometrium, and unaffected or normal peritoneum from patients with (n = 12) and without (n = 14) clinically apparent endometriosis was examined by in situ hybridization and immunocytochemistry analyses. The results showed that the peritoneal biopsies with visible or microscopic endometrial implants contain receptor mRNA and receptor protein. The glands contain more receptor mRNA and receptor protein than stromal cells in implants similar to uterine endometrium from patients with or without endometriosis. However, there is no consistent difference in the expression of receptors in implants compared to uterine endometria from patients with or without endometriosis. Contrary to ectopic endometrial implants, unaffected or normal peritoneum contain neither receptor mRNA nor receptor protein. In summary, we conclude that ectopic endometrial implants contain hCG/LH receptor mRNA and receptor protein, which suggests new possibilities in the medical treatment of endometriosis.     

Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis

Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.     

Interleukin-1 (IL-1) regulation of human endometrial function: presence of IL-1 receptor correlates with IL-1-stimulated prostaglandin E2 production

Previous studies suggest that prostaglandin E2 (PGE2) is important in normal endometrial function and that it may be involved in certain uterine dysfunctions. In this study, the ability of the purified E. coli-derived recombinant interleukin-1 alpha (rIL-1 alpha) to regulate the production of PGE2 by the endometrial epithelium is investigated. PGE2 levels determined by the RIA consistently increase upon incubation of cultured glandular epithelial cells with rIL-1 alpha. A significant increase is obtained with 17 and 170 ng/L rIL-1 alpha. A maximal effect is obtained within 24 h of incubation with rIL-1 alpha. In the seven endometria evaluated, rIL-1 alpha increases PGE2 synthesis in all cases, but the maximal increase relative to the basal levels varies between 2- to 10-fold for a given preparation. Vibratome sections retaining the integrity of the endometrial tissue also show an increased PGE2 synthesis in response to rIL-1 alpha. rIL-1 alpha-stimulated PGE2 production is blocked by the addition of a neutralizing antibody to rIL-1 alpha. In addition, indomethacin, a cyclooxygenase inhibitor, suppresses both rIL-1 alpha-induced and basal PGE2 synthesis. Experiments using radioiodinated rIL-1 alpha reveal that the membranes prepared from human endometrial epithelium possess high affinity receptors for IL-1, suggesting that IL-1 regulates PGE2 synthesis by binding to this receptor site. The expression of IL-1 receptors and the ability to modulate PGE2 production by IL-1 in endometrial epithelium suggest that IL-1 may play a significant role in human uterine function via modulation of PGE2 production.