Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease.

Endometriosis affects women of reproductive age, causing infertility and pain. Although immune cells are recruited in endometriotic lesions, their role is unclear. Tie2-expressing macrophages (TEMs) have nonredundant functions in promoting angiogenesis and growth of experimental tumors. Here we show that human TEMs infiltrate areas surrounding newly formed endometriotic blood vessels. We set up an ad hoc mouse model in which TEMs, and not Tie2-expressing endothelial cells, are targeted. We transplanted in wild-type recipients bone marrow cells expressing a suicide gene (Herpes simplex virus type 1 thymidine kinase) under the Tie2 promoter/enhancer. TEMs infiltrated endometriotic lesions. TEM depletion by ganciclovir administration arrested the growth of established lesions, without toxicity. Lesion architecture was disrupted, with: i) loss of glandular organization, ii) reduced neovascularization, and iii) activation of caspase 3 in CD31(+) endothelial cells. Thus, TEMs are important for maintaining the viability of newly formed vessels and represent a potential therapeutic target in endometriosis.

Continuous low-dose oral contraceptive in the treatment of colorectal endometriosis evaluated by rectal endoscopic ultrasonography.

OBJECTIVE: Limited attention has been focused on the medical treatment of bowel endometriosis. This study evaluates the efficacy of administration of a continuous low-dose oral contraceptive in treating pain and other symptoms associated with colorectal endometriotic nodules, as evaluated by rectal endoscopic ultrasonography. DESIGN: Prospective observational study. SETTING: Academic Department of San Raffaele Scientific Institute, Obstetrics and Gynecology Unit. POPULATION: Symptomatic women of reproductive age (n=26) with colorectal nodules infiltrating at least the bowel muscularis propria and without a stenosis >50%. In 31% of the patients, endoscopic ultrasonography permitted diagnosis of nodules located more than 10 cm from the anal rim. METHODS: Patients received a continuous low-dose oral contraceptive containing 15 µg ethinylestradiol and 60 µg gestodene for 12 months. Subjective symptoms were prospectively evaluated, and nodule volumes were monitored using endoscopic ultrasonography. MAIN OUTCOME MEASURES: Nodule measurements were performed at baseline and after 12 months of treatment. Symptoms at the start and after 12 months were evaluated. RESULTS: A significant improvement in the intensity of all the considered symptoms (dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia and painful defecation) was seen when evaluated by a visual analog scale. A reduction in terms of both diameter (mean reduction 26%) and volume of the nodules (mean reduction 62%) was observed after a 12 month period. CONCLUSIONS: A continuous low-dose oral contraceptive therapy may reduce bowel endometriosis-associated symptoms. In addition, this therapy induces a significant volumetric reduction of colorectal plaques when evaluated by endoscopic ultrasonography.

Endoscopic rectal ultrasound and elastosonography are useful in flow chart for the diagnosis of deep pelvic endometriosis with rectal involvement.

AIM: Endometriosis is defined by the presence of endometrial glands and stroma outside the uterus. The disease causes pelvic pain, dysmenorrhea, dyspareunia, dyschezia and urinary symptoms. The aim of this study was to assess the usefulness of endoscopic ultrasound (EUS) and elastosonography for detecting rectosigmoid endometriosis and to compare the findings, in selected and symptomatic patients, with surgical specimens in order to select the best surgical strategy. MATERIAL & METHODS: Sixty-three consecutive patients (mean age 34.2; range 25-50 years) with diagnosis of endometriosis were referred for rectal endosonography to evaluate the rectal involvement. Patients complained of abdominal pain, rectal bleeding, constipation and dysmenorrhea. Sub-stenosis of the rectosigmoid lumen was found endoscopically in one patient (1.5%), bulging in 21 (33.3%), mucosal hyperemia or edema in one (1.5%), and no lesions in 39 patients (61.9%); no abdominal masses or obstruction were reported. Each woman completed a self-administered 100-point questionnaire to evaluate endometriosis-related pain (intensity of symptoms: 0 = absent, 100 = unbearable). After clinical imaging evaluation, 10 symptomatic patients (mean age 32.2; range 26-45 years) were evaluated for surgery. RESULTS: EUS detected endometriotic lesions in all patients as a hypoechoic mass, poorly vascularized with irregular, undefined margins. In cases where the rectosigmoid wall was involved, there was invasion of the fourth layer. All patients who were operated had histologic findings of endometriotic lesions involving the rectal wall, as indicated by EUS. CONCLUSION: EUS and elastosonography offers a non-invasive and sensitive technique to better define the endometriotic infiltration in the rectosigmoid wall.

Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease.

The mechanisms that sustain endometrial tissues at ectopic sites in patients with endometriosis are poorly understood. Various leukocytes, including macrophages, infiltrate endometriotic lesions. In this study, we depleted mouse macrophages by means of either clodronate liposomes or monoclonal antibodies before the injection of syngeneic endometrial tissue. In the absence of macrophages, tissue fragments adhered and implanted into the peritoneal wall, but endometriotic lesions failed to organize and develop. When we depleted macrophages after the establishment of endometriotic lesions, blood vessels failed to reach the inner layers of the lesions, which stopped growing. Macrophages from patients with endometriosis and experimental mice, but not nonendometriotic patients who underwent surgery for uterine leiomyomas or control mice, expressed markers of alternative activation. These markers included high levels of scavenger receptors, CD163 and CD206, which are involved in both the scavenging of hemoglobin with iron transfer into macrophages and the silent clearance of inflammatory molecules. Macrophages in both inflammatory liquid and ectopic lesions were equally polarized, suggesting a critical role of environmental cues in the peritoneal cavity. Adoptively transferred, alternatively activated macrophages dramatically enhanced endometriotic lesion growth in mice. Inflammatory macrophages effectively protected mice from endometriosis. Therefore, endogenous macrophages involved in tissue remodeling appear as players in the natural history of endometriosis, required for effective vascularization and ectopic lesion growth.

Premature ovarian failure in suspected Whipple's disease.

INTRODUCTION: Whipple's disease is a relapsing systemic infectious disease probably caused by the Gram-positive bacillus Tropheryma whippelii. The diagnosis can be established based on the characteristic histopathological features found in the affected organ (foamy macrophages with a coarsely granular cytoplasm, which stains with PAS, and by means of polymerase chain reaction (PCR) technology). CASE REPORT: We report a case of a 23-year-old woman affected by suspected Whipple's disease. She presented encephalopathy and neuropathy with inveterate hyperpyrexia and alteration of the hypothalamic-pituitary-ovary axe. She was amenorrheic because of an hypergonadotropic hypogonadism. DISCUSSION: This hypogonadism is possibly due to follicular depletion caused by inveterate hyperpyrexia or T. whipplii localization.