Frank Oehmke

Role of TGF-βs in normal human endometrium and endometriosis

Endometriosis is characterized by presence of endometrial tissue outside the uterus. Prevalence is estimated at 6-10% in the general female population and many patients experience pain and/or infertility. Diagnosis is achieved by laparoscopic intervention followed by histological confirmation of viable endometriotic tissue. Mild cases are managed medically with contraceptive steroids and non-steroidal anti-inflammatory agents. Surgery provides relief to women in pain but symptoms recur in 75% of cases within 2 years. Starting with menstruation, we have categorized endometriosis into six stages, namely (1) shedding of cells, (2) cell survival, (3) escape from immune surveillance, (4) adhesion to peritoneum, (5) angiogenesis and (6) bleeding. In most of these biological processes, which resemble metastasis, transforming growth factor-beta (TGF-betas) and their high-affinity receptors are involved directly or indirectly. TGF-betas are abundantly and differentially expressed in the endometrium under hormonal control. Although they are preferentially synthesized in the stroma, glands and macrophages also secrete TGF-betas into the uterine fluid, where interaction with preimplantation embryos is suspected. Because mRNA and protein expression of all three TGF-betas is increased around menstruation, we suggest that TGF-betas might be involved in initiation of menstruation. Furthermore, because of high postmenstrual TGF-beta3 levels, we suppose that it might participate in scarless postmenstrual regeneration of endometrium. Our suggestions pave the way to novel routes of investigation into the roles of TGF-betas during menstruation and endometriosis.

Impact of endometriosis on quality of life: A pilot study

Endometriosis affects 6–10% of women in reproductive age, 35–50% of whom experience pain, infertility or both. Mild cases are managed medically but surgery provides relief to women in pain. However, symptoms recur in 75% of cases within 2 years. We investigated the impact of endometriosis on quality of life among 65 women aged 18–60 years working at a city supermarket in Giessen, Germany. Of the 65 women, 12 had undergone surgeries, 22 had dysmenorrhoea, 24 dyspareunia and 3 were infertile. Of the 22 women with dysmenorrhoea, 10 had difficulties performing gardening, housework, sports and leisure activities. Five of these 10 women experienced social isolation, 6 professional setbacks; 6 declined efficiency at work and 3 had taken time off work. Of the 24 women with dyspareunia, 7 experienced minimal, 12 light and 5 moderate to strong pain. Only 16 of these 24 women discussed the problem with their partners. This study demonstrates that pain is a major cause of physical, psycho-social, emotional and professional or work related impairment among women with endometriosis. Because endometriosis is likely to impose emotional and financial burdens, we suggest that future studies should be extended to include interviews with family members.

Association of neutrophil extracellular traps with endometriosis-related chronic inflammation.

OBJECTIVE To study if neutrophil extracellular traps (NETs) are present in the peritoneal fluid of endometriosis patients. NETs play a crucial role in fighting against microorganisms. However, exaggerated NET production may lead to tissue damage in their vicinity in pathological conditions. Our study evaluates the presence of NETs in endometriosis peritoneal fluid. STUDY DESIGN Peritoneal fluid (PF) was collected in a case-control study from 52 women, who underwent either diagnostic or operative laparoscopy. The control group consisted of 17 women with infertility, chronic pelvic pain, simple or functional cysts or irregular bleeding. The endometriosis group, altogether 35 patients, comprised 19 patients with stage I and II and 16 patients with stage III and IV endometriosis. First we tested whether the PF is able to stimulate NET production. Neutrophils from healthy volunteers were treated with the PF of endometriosis patients and controls and NETs were detected with Sytox orange extracellular DNA dye and immunofluorescence microscopy. Then we evaluated if NETs were already present in the collected PF using the specific myeloperoxidase (MPO)-DNA capture ELISA method, based on the MPO associated with the NET scaffold. RESULTS The PF of endometriosis patients did not stimulate NET release from healthy granulocytes. However, pre-existent NETs could be detected in 17 endometriosis patients out of 35 (49%). In contrary, in the control group NETs were present in only 3 patients out of 17 (18%), (p=0.03, OR: 4.4). Moreover, the quantification of NETs showed a significantly higher amount of NETs in endometriosis compared to the controls (0.097 vs. 0.02, p=0.04). CONCLUSION This is the first study, which evaluated and described the presence of NETs in the PF of endometriosis patients. Our study shows, that NETs may be involved in the complex pathophysiology of endometriosis.

Laparoscopic myomectomy in patients with uterine myomas associated with infertility.

Abstract Although myomectomy is widely accepted in women of childbearing age who wish to retain their fertility, the extent to which myomas affect fertility and whether their removal improves this remain unclear. This study aimed to elucidate the favourable surgical approach in women with uterine myomas and infertility. This retrospective, follow-up study was carried out in three centres in Germany. Data on women who had undergone myomectomy via laparoscopy, laparotomy or conversion to laparotomy in 2000–04 were collected and analysed. Fertility outcome after myomectomy was assessed by follow-up postal questionnaire in a subgroup of women with myoma-associated infertility. Data on 159 women with otherwise unexplained infertility were included (mean age 35 years (range 17–47), mean number of myomas 2.4 (range 1–8) and mean myoma size 6.1 cm (range 0.5–20)). Women who underwent laparoscopy had fewer complications. 39.6% (63/159) of women completed the questionnaire, which showed that the pregnancy rate after myomectomy was 46% in this group. No uterine rupture occurred. Laparoscopy is associated with fewer postoperative complications and since no preoperative or intraoperative factors seem to influence the fertility outcome in women with uterine myomas, it is the treatment of choice in these patients.

Transvaginal NOTES with semi-rigid and rigid endoscopes that allow adjustable viewing angles

PurposeTo evaluate semi-rigid and rigid endoscopes for transvaginal NOTES surgery.MethodsOne rigid endoscope (EndoCAMeleon, KARL STORZ GmbH & Co. KG, Tuttlingen Germany) and one semi-rigid endoscope (EndoEYE LTF-VH, Olympus Deutschland GmbH, Hamburg, Germany) that allow adjustable viewing angles have been used during four transvaginal gynecological NOTES procedures for chronic pelvic pain and infertility.ResultsFeasibility of transvaginal access to enter the abdominal cavity was shown. Posterior peritoneum, ovaries and tubal patency were evaluated. The evaluated endoscopes did not overcome the inability to explore the anterior pelvic structures.ConclusionsRigid and semi-rigid endoscopes that allow adjustable viewing angles during transvaginal NOTES approaches cannot explore the whole pelvic anatomical structures.

A new variable-view rigid endoscope evaluated in advanced gynecologic laparoscopy: a pilot study.

BackgroundThis pilot study aimed to evaluate the optical performance and clinical handling of a new variable-view rigid endoscope with angulation from 0º to 120º in gynecologic laparoscopic surgery.MethodsThe EndoCAMeleon endoscope was assessed by experienced surgeons and assistants during a variety of advanced gynecologic laparoscopic procedures. After each procedure, both the surgeon and the assistant each completed questionnaires designed to assess the endoscope’s ease of handling and optical performance.ResultsThe endoscope was assessed during 21 advanced procedures. Questionnaire responses confirmed surgeon and assistant satisfaction with the mechanical handling and vision provided by the endoscope. In particular, the ability to vary the viewing angles enabled the surgeon to visualize the surgical site without moving the endoscope shaft.ConclusionsThe new endoscope performed well in the hands of experienced surgeons and assistants undertaking advanced procedures. The variable-view rigid endoscope allows the use of visual ports during primary port entry and enhances vision. Further study is required to evaluate its performance in routine practice.

Management of adult primary vulvar Langerhans cell histiocytosis: review of the literature and a case history

Primary vulvar Langerhans cell histiocytosis (LCH) is extremely rare and there are no standard treatment options. This review of the published literature with a case report aimed to clarify the optimal treatment for patients with this condition. Medline and PubMed were searched and all cases of primary vulvar LCH reported as single case reports or small case series were reviewed. A patient with vulvar LCH treated in this department is also reported. Twenty-seven cases, including the reported case, were reviewed. First-line treatments included surgery, radiotherapy, chemotherapy, thalidomide and local treatment. The mean follow-up time was 21.1±17.7 months. Although no patient died from the disease, recurrence rates were high (62%) and the mean time to relapse was 10.9±11.8 months (range 1-36 months). Treatment with thalidomide was successful, resulting in long-lasting remission. Disease recurrence is likely after surgery and or radiotherapy, and these treatments together with chemotherapy affect the patients wellbeing adversely. Although definitive conclusions await further work, thalidomide has minimal adverse effects, is easy to administer and should be considered as a first-line treatment or as maintenance therapy in some patients.

The analysis of the human plasma N-glycome in endometriosis patients

OBJECTIVE Analysis of the plasma N-glycome in endometriosis patients compared with controls. STUDY DESIGN In a case-control study, blood samples were collected from patients who underwent either diagnostic or operative laparoscopy between 2008 and 2011 in the Semmelweis University, Budapest, I. Department of Obstetrics and Gynaecology. From these patients, 92 with endometriosis (30 stage I-II and 62 stage III-IV, including altogether 18 deep infiltrating cases) and 62 controls were selected for glycan analysis. After release, plasma N-glycans were subjected to hydrophilic interaction high performance liquid chromatography, which resulted in 19 chromatographic glycan peaks (GP). The abundances of the GPs were compared between the study groups. For statistical analysis a non-parametric test, the Mann-Whitney-U test, was used. RESULTS We found a statistically significant decrease of GP1 and increase of GP14, GP17 and GP18 in endometriosis patients. The latter peaks consist of glycans which play a role in inflammatory processes and malignancy. We also found significant differences in GP2, GP4, GP6, and GP9 between controls and the different endometriosis stage groups. The observed alterations in GP2, GP4 and GP6 may be related to altered glycosylation and remodelling of the glycan branches of the IgG molecule. The alterations of GP9 are presumably associated with changes of transferrin glycosylation. Furthermore we detected a highly significant decrease of GP1 in patients with deep infiltrating endometriosis compared with controls. CONCLUSIONS This is the first analysis of the plasma N-glycome in endometriosis. The observed changes in GP14, GP17 and GP18 and in GP2, GP4, GP6 and GP9 provide new aspects to the pathophysiology of the disease and the alterations of the GP1 may serve as a new potential marker in the future.

Feasibility of laparoscopic management of acute haemoperitoneum secondary to ruptured ovarian cysts in a haemodynamically unstable patient.

Abstract Acute haemoperitoneum in patients with coagulation disorders or those under anticoagulation therapy is a diagnostic and therapeutic dilemma. Since radiological imaging is often insufficient for establishing the origin of the bleeding, a laparoscopic approach can be considered before a laparotomy is performed in haemodynamically unstable patients. A 32-year-old woman receiving coumadin therapy presented with acute lower abdominal complaints. Due to suspicion of a tubo-ovarian abscess after the initial ultrasound, a conservative treatment was administered. A routine blood count after 12 hours showed a significant reduction in haemoglobin. During the CT scan, the patient developed unstable haemodynamics. Based on deteriorating coagulation parameters, mass transfusion and stabilization of the coagulation were performed but were not successful. Therefore an interventional laparoscopy was performed and a ruptured ovarian cyst was found to be the cause of bleeding. A ruptured ovarian cyst might be the cause of an acute abdomen and haemoperitoneum in young women. Therefore cyclus anamnesis and the exclusion of other obvious reasons for acute mass bleeding, i.e. ectopic pregnancy, can justify the laparoscopic approach after stabilization of the coagulation parameters. Long-term combined oral contraceptive therapy is indispensable for the prevention of these sorts of bleeding complications.

A structured questionnaire improves preoperative assessment of endometriosis patients: a retrospective analysis and prospective trial

PurposeTo determine whether a structured questionnaire can improve preoperative assessment of patients with endometriosis.MethodsHospital records for patients with endometriosis were evaluated retrospectively to determine the completeness of information. A structured electronic questionnaire was developed and used to assess preoperatively patients with suspected or proved endometriosis. Data from both assessments were compared.ResultsData analysed retrospectively showed that there were valid answers for 89.2% of questions on a standard patient history template, but information was available for only 46.3% of parameters considered specific to endometriosis. Data from 69 patients investigated by structured electronic questionnaire gave improved rates of 90.3% for standard patient history items and 88.5% for endometriosis-specific parameters. Significant improvement in valid answers was achieved in 66.7%.ConclusionsA structured questionnaire improved the documentation of endometriosis-specific parameters. Further studies are needed to ensure that it enhances the effectiveness of preoperative counselling and decisions about surgery.