Endometriosis: Kimmig R

Fink D, Lang U, Kimmig R. · No affiliation provided · Gynakol Geburtshilfliche Rundsch. · Pubmed #17641472 No free full text.

Abstract: Endometriosis is one of the most frequent gynecological disorders. The diagnosis is usually confirmed by laparoscopy. As the etiology and pathogenesis of endometriosis are still mostly obscure, a causal therapy has not been found yet. As for the medicinal treatment of endometriosis, all modern therapeutic approaches aim at ovarian downregulation or at antagonizing the estrogen effects in the endometriosis focus. Surgery aims at a preferably complete resection of all endometriosis focuses. In addition to individual distress, the economic aspect must not be neglected because of its high morbidity, loss of workforce and the repeated therapeutic interventions. As treatment strongly depends on the specific complaints and the personal life circumstances of the patient, an individual therapy concept should always be considered.

Boing C, Kimmig R. · Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Duisburg-Essen, Essen, Germany. · Gynakol Geburtshilfliche Rundsch. · Pubmed #17641475 No free full text.

Abstract: Laparoscopy is the treatment of choice in the diagnostics of endometriosis. Surgical management of early-stage endometriosis at the time of diagnosis is to be aimed at. Resection of peritoneal endometriosis is essential; coagulation/ablation may be an alternative. In the early stages, pain reduction is as effective as by drug therapy. Surgery improves fertility in these stages. Complete removal of an endometrioma lowers the recurrence rate and improves fertility. In cases of definitive surgical therapy, i.e. hysterectomy and adnexectomy, any accompanying endometriosis focuses have to be carefully resected. When clinically symptomatic, a deep endometriosis has to undergo radical surgery. In these cases, assisted reproduction is usually necessary when such a patient wants to become pregnant. The recurrence rate after complete surgical management of a serious endometriosis is lower compared to drug therapy; pain reduction is more effective. A postoperative drug therapy with GnRH analogues, danazole or gestagen does not improve fertility, the interval to a recurrence is however positively influenced. Hormonal replacement therapy after definitive surgical management has probably no influence on the recurrence rate.

Hauth EA, Stattaus J, Kimmig R, Schmidt M, Forsting M. · Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinkum Essen. · Zentralbl Gynakol. · Pubmed #15800838 No free full text.

Abstract: Widely accepted as an established method in the diagnostic imaging of diseases of the female pelvis, magnetic resonance imaging (MRI) holds promising potential for the diagnosis of endometriosis. This review describes the general prerequisites for performing MRI scans of the pelvis and presents, based on recent studies, an imaging protocol suited to the diagnosis of endometriosis. Typical manifestations and sites of endometriosis are discussed and illustrated with sample images. For endometriotic cysts and implants, axial T (1)-weighted, fat-saturated turbo spin echo sequences (TSE) have the highest diagnostic value. In diagnosing adenomyosis, sagittal T (2)-weighted TSE sequences visualise changes in the uterine zonal anatomy. In essence, MRI is capable of detecting many manifestations of endometriosis in a non-invasive, yet reliable manner, and its value in relation to laparoscopy must be considered as complementary.

Allhorn S, Böing C, Koch AA, Kimmig R, Gashaw I. · Institute of Anatomy II, University of Duisburg-Essen, Essen, Germany. · Reprod Biol Endocrinol. · Pubmed #18775079 links to  free full text

Abstract: BACKGROUND: Toll-like receptors (TLRs) play an essential role in the innate immune system by initiating and directing immune response to pathogens. TLRs are expressed in the human endometrium and their regulation might be crucial for the pathogenesis of endometrial diseases. METHODS: TLR3 and TLR4 expression was investigated during the menstrual cycle and in postmenopausal endometrium considering peritoneal endometriosis, hyperplasia, and endometrial adenocarcinoma specimens (grade 1 to 3). The expression studies applied quantitative RT-PCR and immunolabelling of both proteins. RESULTS: TLR3 and TLR4 proteins were mostly localised to the glandular and luminal epithelium. In addition, TLR4 was present on endometrial dendritic cells, monocytes and macrophages. TLR3 and TLR4 mRNA levels did not show significant changes during the menstrual cycle. In patients with peritoneal endometriosis, TLR3 and TLR4 mRNA expression decreased significantly in proliferative diseased endometrium compared to controls. Interestingly, ectopic endometriotic lesions showed a significant increase of TLR3 und TLR4 mRNA expression compared to corresponding eutopic tissues, indicating a local gain of TLR expression. Endometrial hyperplasia and adenocarcinoma revealed significantly reduced receptor levels when compared with postmenopausal controls. The lowest TLR expression levels were determined in poor differentiated carcinoma (grade 3). CONCLUSION: Our data suggest an involvement of TLR3 and TLR4 in endometrial diseases as demonstrated by altered expression levels in endometriosis and endometrial cancer.

Gashaw I, Stiller S, Böing C, Kimmig R, Winterhager E. · Institute of Anatomy, University of Duisburg-Essen, 45122 Essen, Germany. · Endocrinology. · Pubmed #18202125 links to  free full text

Abstract: The pro-angiogenic factor cysteine-rich protein 61 (CYR61/CCN1) mediates different signals in tumorigenesis, angiogenesis and is involved in the pathogenesis of endometriosis. In this study we investigated the temporal and spatial expression pattern in human endometrium during the menstrual cycle and its possible regulation mechanisms in the premenstrual phase. CYR61 transcript expression showed two distinct periods of elevated levels in the proliferative phase and in menstrual effluents. Because the menstrual breakdown of the functionalis is triggered by cytokines, prostaglandins (PGs), as well as hypoxia, we used a benign endometrial cell line to investigate if CYR61 is regulated by these factors. Hypoxic conditions transiently induced CYR61 mRNA levels and enhanced the secretion of the CYR61 protein into the medium. The hypoxia-inducible factor (HIF) 1alpha mediated this effect on CYR61 as evidenced by dimethyloxalylglycine treatment and by HIF1alpha short interfering RNA. CYR61 mRNA expression was further regulated by IL-1, TNFalpha, PGE2, and PGF2alpha. In addition, TNFalpha and PGE2 elevated significantly CYR61 cellular protein levels in well-oxygenated cells but had only a slight effect on the quantity of secreted protein. Moreover, PGE2 combined with hypoxic conditions increased CYR61 mRNA and protein levels synergistically, whereas the combination with TNFalpha abolished the CYR61 levels induced by hypoxia. Together, the up-regulation of CYR61 by hypoxia via HIF1alpha, TNFalpha, and PGE2 could represent possible mechanisms for the CYR61 increase at the onset of menstruation. The opposite effect of TNFalpha combined with hypoxia on CYR61 up-regulation could contribute to a balanced expression level of this angiogenic factor in the endometrium.

Fechner S, Husen B, Thole H, Schmidt M, Gashaw I, Kimmig R, Winterhager E, Grümmer R. · Institute of Anatomy, University Hospital Essen, Universität Duisburg-Essen, Essen, Germany. · Fertil Steril. · Pubmed #17316633 No free full text.

Abstract: OBJECTIVE: To investigate the regulation of estrogen-converting enzymes in human ectopic endometrial tissue. DESIGN: Animal study. SETTING: Academic medical center. ANIMAL(S): Sixty female nude mice with implanted human endometrial tissue. PATIENT(S): Twenty-two premenopausal women undergoing endometrial biopsy or hysterectomy. INTERVENTION(S): Human endometrial tissue was implanted into the peritoneal cavity of nude mice, and the effect of therapeutic drugs on transcription of steroid receptors and estrogen-converting enzymes was analyzed. MAIN OUTCOME MEASURE(S): Transcript levels of steroid hormone receptors, 17beta-hydroxysteroid dehydrogenase type 1 and 2, aromatase, and steroid sulfatase as well as proliferation rate were analyzed in the human ectopic endometrial tissue. RESULT(S): Steroid receptors and estrogen-converting enzymes were expressed in the ectopic human endometrial fragments. Application of medroxyprogesterone acetate, dydrogesterone, danazol, and the aromatase inhibitor finrozole significantly inhibited aromatase transcription. In addition, danazol caused a significant decrease in transcription of steroid sulfatase, and finrozole, of 17beta-hydroxysteroid dehydrogenase type 1 in parallel to a decrease in proliferation rate in the ectopic human endometrial tissue. CONCLUSION(S): Pharmacological regulation of transcription of estrogen-converting enzymes in human endometrium cultured in nude mice may help to develop new therapeutic concepts based on local regulation of estrogen metabolism in endometriosis.

Hauth EA, Antoch G, Ruehm SG, Böing C, Kimmig R, Forsting M. · Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Essen. · Rofo. · Pubmed #15346261 No free full text.

Abstract: PURPOSE: To determine the value of magnetic resonance imaging (MRI) of the pelvis in the preoperative diagnosis of endometriosis. MATERIALS AND METHODS: Over a period of 8 months, preoperative MRI of the pelvis were obtained in 13 patients with suspected endometriosis (mean patient age 34.6 years; range 25 - 47 years). RESULTS: In 9 of 13 patients (69 %), the diagnosis of endometriosis was made by MRI and confirmed by laparoscopy in 8 cases. In 2 of 13 patients, endometriotic lesions were detectable by laparoscopy only. In the remaining 2 patients, no endometriosis was visible on MRI or by laparoscopy. MRI was able to visualize a total of 19 endometriotic lesions, with 14 (74 %) confirmed by histopathologic examination following laparoscopy. Five of these 19 lesions (26 %) visible on MRI were not seen by laparoscopy. Using laparoscopy and subsequent histopathologic examination, 27 endometriotic lesions were diagnosed, with 13 (48 %) not seen on the preoperative MRI. CONCLUSION: MRI and laparoscopy are complementary diagnostic tools that will best document the full extent of endometriosis when combined. MRI can visualize additional lesions inaccessible to laparoscopy. Thus, MRI of the pelvis should used preoperatively for surgical treatment planning.