Congresses

7. German Endometriosis Congress 2007
   Conference chair: Prof. Dr. med. A.D. Ebert
   Date: September 26 – 29, 2007
   Conference venue: Berlin, Hotel Berlin, Lützowplatz 17, 10785 Berlin

Title: “Endometriosis, Uterus & Fertility”

Information:
Conventus Congressmanagement & Marketing GmbH,
Market 8; 007743 Jena
Tel: +49 3641 35 33 22 31
katharina.kaps@conventus.de
www.conventus.de/endometriose

Greetings from the President:
Diagnosis of endometriosis – what does this mean for a woman’s life and what has already preceded this diagnosis?
Endometriosis is a benign gynecological disease that is primarily associated with increased menstrual pain, possibly also increased bleeding, lower abdominal pain and discomfort, but also pain during bowel movements, urination or sexual intercourse. It is often also associated with involuntary childlessness. These symptoms do not usually occur together, but combinations of different symptoms may be present in one patient. It is therefore always important to remember that menstruation that leads to feeling ill, bedridden or abusing medication is not normal and may be the first sign of endometriosis, i.e. ultimately a disease of the uterus and its appendages.
Unfortunately, the diagnosis is often made far too late. There is good data from America and England which shows that in these countries the diagnosis is not actually established until 6 to 8 years after the first symptoms. During this time, this benign disease can of course continue to grow and the symptoms can become chronic. In many cases, patients have already undergone surgery or hormonal treatment. Hormone treatment with the pill or GnRh analogs in particular is highly effective, but means that the fine-tuning of the body is also interfered with, which is unfavorable if you do not know what the disease actually is. A suspected diagnosis of endometriosis alone does not justify starting treatment with highly effective hormone preparations. It makes sense to aim for histologic confirmation, and the gold standard here is still laparoscopy, where the disease can not only be clearly diagnosed, but where samples can also be taken and the endometriosis should be completely removed with scissors, ultrasound or laser if possible. At the same time, the patency of the fallopian tubes can be checked and the uterus scanned for abnormalities.
As in any field of medicine, it is clear that the greatest risk factor for a disease is always the first doctor or surgeon to treat it. For this reason, it is now generally accepted in Germany that endometriosis operations are by no means beginners’ operations, but that, particularly in the case of extensive endometriosis, surgery is only comparable to extensive ovarian carcinoma operations in terms of technical requirements. In any case, the increasing amount of information available to women, particularly via magazines, newspapers and the Internet, is also raising awareness of the topic of endometriosis, which also applies to the medical profession. Self-help groups disseminate their experiences, congresses pass them on to specialist colleagues, and cooperation with the research-based pharmaceutical industry is essential because, in addition to new quality assurance concepts, new drugs are also needed to optimize the treatment of endometriosis or even its early detection.
Endometriosis is now regarded as a benign disease. However, if you look at the spread patterns, i.e. the sites of colonization and the biological behaviour of this disease, you cannot help but notice that there may be some similarities to diseases of an invasive nature. Endometriosis forms new vessels, new nerve sprouts take place, the cells can proliferate hormone-dependent and hormone-independent, attach themselves to other organs and grow into them – these are characteristics that we otherwise only know from tumors, and which in some cases, e.g. in the case of bowel or bladder infestation, also lead to extensive operations.
Regardless of this, endometriosis is not a cancer. This interface between benignity and malignancy is the starting point for many research projects that have developed in recent years under the collective term “translational research”. Hormone receptors, the expression of nerves and other growth factors, signal transduction within endometriosis cells, their hormone dependency, their biological invasion behavior and many other biological factors are currently being investigated with regard to their usefulness for new diagnostic or therapeutic procedures.
The number of publications on endometriosis in the fields of clinical and basic research is steadily increasing, reflecting an awareness of the problem among clinical and experimental researchers. This development must be supported at all costs, as new approaches must be pursued or created in all areas of research. On the one hand, this concerns the basic research already mentioned, applied basic research, clinical research, the investigation of new diagnostic possibilities, but also the investigation of quality of life, sexuality, psychosomatic changes through to questions of rehabilitation and reintegration, the chronification of pain and the desire to have children.
These areas require broad social support, which can be provided not only by research or industry, or by clinics and self-help groups, but also by health policy in particular. It must be made clear that the problem of endometriosis is a problem for society as a whole, and that all those involved should work as partners towards one goal – the eradication of this disease through prevention. Politicians and health insurance companies in particular have a key role to play here, as these institutions are located at interfaces that enable coordination and the pooling of forces.
The financial background for research into this enigmatic disease is still extraordinarily low when compared with oncological diseases. However, it should be noted that clinical pictures cannot be weighed up against each other. However, if we assume that there are 1.5 to 2 million patients with endometriosis and that at least 30 percent of these cases result in more than 10 days of absence from work per year, if we take into account that 1000 patients with a diagnosis of endometriosis are operated on in Berlin alone and if we consider that this disease can certainly be understood as a chronic disease, it quickly becomes clear that there has clearly been too little initiative and commitment to endometriosis to date.
It is clearly to be hoped that task forces will be formed on the part of those politically responsible, health insurance companies, industry, self-help groups, rehabilitation facilities and clinical and basic researchers to coordinate the quality of diagnostics and treatment, as well as research in all areas, in cooperation with the Scientific Endometriosis Foundation, the European Endometriosis League, the Endometriosis Association Germany and other working groups.
The 7th German Endometriosis Congress offers an excellent platform for this.
The first independent steps have already been taken by those affected and the doctors who deal with endometriosis. In this context, reference should be made to the development of quality criteria for certification as an endometriosis center at various levels and the development of guidelines for the diagnosis and treatment of endometriosis. These steps must now also be supported economically by other partners. It is an anachronism that in 21st century Europe millions of women still suffer from a benign disease that prevents them from enjoying their best years in terms of quality of life, the possibility of having children, actively participating in society or living out their sexuality. The European Parliament has already taken a position on this and found partners from the medical sector. These steps in particular indicate that there is a pronounced need for action in Germany in order to expand the good potential that already exists in an exemplary manner across Europe.

1. Poster Prize Congress 2007

The following works were awarded poster prizes:

1. The safety of laparoscopically assisted uterine biopsy (LAUB) for the intraoperative diagnosis of adenomyosis uteri
   Dakkak^R1, Stein ^S-E1, Mechsner ^S2, Herbst ^H1, Halis ^G2, Ebert ^AD1/2

1) Endometriosis Center Berlin Level III, Clinic for Gynaecology and Obstetrics, Vivantes-Humboldt-Klinikum, Am Nordgraben 2, 13509 Berlin; 2) Endometriosis Center Charite, CBF, Hindenburgdamm 30, 12200 Berlin

Objective: Adenomyosis uteri is currently a diagnostic and therapeutic problem. The aim of the study was to evaluate the safety of laparoscopically assisted uterine biopsy.

Material and methods: A retrospective analysis of 73 patients who underwent surgery in our clinic between April 2006 and March 2007 and were biopsied using a Bard magnum biopsy needle in the sense of a LAUB was performed. Adenomyosis uteri was suspected in all patients on the basis of medical history, preoperative examinations and/or intraoperative macroscopic findings. Postoperatively, vaginal ultrasonography was performed to rule out an intramural hematoma.

Results: An average of 2-3 punch cylinders were removed per patient. They received an average of 6 I.U. (0 – 12 I.U.) of oxytocin. Histological evidence of adenomyosis was found in 13 of the 72 patients (18%). Detection was successful for rASRM stage I in 23%, for stage II in 8%, for stage III in 38% and for stage IV in 8% of cases. In two patients (3% of the total collective), a small, clinically irrelevant hematoma of the uterine wall was diagnosed postoperatively. Temperatures or bleeding did not occur.

Conclusion: In principle, laparoscopically assisted uterine biopsy can be regarded as a safe, simple procedure for the histologic confirmation of adenomyosis uteri. Further options must be evaluated in order to increase the accuracy and thus the informative value. Preoperative MRI examinations or intraoperative vaginal sonography could be considered.
Literature/correspondence: andreas.ebert@vivantes.de

2. Stage-appropriate surgery for intestinal endometriosis

Frevel ^AK1, Tank ^M1, Probst ^W2, Schweppe ^{K-W1 1Ammerlandklinik}GmbH, Women’s Clinic, Westerstede; ^{2Ammerlandklinik}GmbH, Department of General Surgery of the Surgical Clinic, Westerstede
Question: Which surgical radicality is necessary for the different degrees of severity of intestinal endometriosis?

Background: The generally accepted classification for endometriosis originates from the ASRM and only takes into account the peritoneal and ovarian forms of the disease, but not the deep infiltrating type. The Scientific Endometriosis Foundation has developed a differentiated classification (Enzian) for these retroperitoneally growing lesions to describe the findings and compare the results of treatment (Tuttlies et al. 2005). We advocate a surgical radicality adapted to the severity of the endometriosis. If the seromuscularis of the colon or the muscularis of the rectum is affected without infiltration of the mucosa, a mucosa-saving resection (MSR) should be attempted. If all layers of the intestinal wall are infiltrated, a “disk resection” should be performed and, in the case of extensive, stenosing involvement, a segmental resection is possible while sparing the mesentery with resection close to the intestinal wall with anastomosis.

Material and methods: The retrospective analysis of 32 surgical reports and histologic findings of patients treated in our clinic between 2006 and 2007 forms the basis of this study. Severity of endometriosis based on the intraoperatively determined Enzian stage, possible multifocality, type of surgery, duration of surgery, intraoperative and postoperative complications were recorded.

Results: Depending on the extent of the intestinal endometriosis (volume of the tumor, lateral extent and caudal extent), a different surgical procedure must be performed. Segmental resection with end-to-end anastomosis (hand-sewn or stapler anastomosis) was performed in 21 cases, disk resection in 3 cases and MSR in 8 patients. This pilot study shows,

1. that the Enzian classification is suitable for site description in clinical practice and should be used for prospective comparative studies of different surgical techniques for deep infiltrating endometriosis, and
2. that an individualized surgical radicality adapted to the severity of the endometriosis is adequate for the treatment of intestinal endometriosis.

Literature: Tuttlies, F., Keckstein, J., Ulrich U, Possover, M, Schweppe, K.-W., Wustlich M. and co-authors: Enzian classification of deep infiltrating endometriosis. Zentralbl. Gynecol. 127(2005)275

3. The role of twist in the invasive growth of endometriosis
   Juelicher^A1, Bartley ^J1, Hotz^B2, Arndt ^M2, Hotz ^H2, Ebert ^AD3
   1Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Clinic for Gynecology with a focus on Gynecologic Oncology, Berlin; ^2Charité– Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Surgery I, Clinic for General, Vascular and Thoracic Surgery, Berlin; ^3VivantesHumboldt-Klinikum, Clinic for Gynecology and Obstetrics, WHO/UNICEF Baby-Friendly Hospital, Endometriosis Center Berlin Level III, Focus on Gynecological Oncology, Berlin
   Introduction: Endometriosis (EM) is a benign disease of women of reproductive age. However, EM shares characteristics with malignant tumors such as potentially invasive and metastatic growth. Epithelial mesenchymal transition (EMT) is an important prerequisite for invasive and metastatic growth of malignant tumors. EMT leads to the dissolution of cell-cell contact: the cells become migratory. An important factor for EMT is the embryonic transcription factor Twist. Twist regulates the expression of the adhesion molecules E- and N-cadherin: the inhibition of E-cadherin and induction of N-cadherin ultimately enable the cells to migrate. N-cadherin expression is associated with an increased invasive and metastatic potential and a worsened prognosis in malignant diseases. Twist expression has already been detected in some malignant tumors, including endometrial carcinoma. Twist and N-cadherin expression will be analyzed by immunohistochemistry (IHC) on EM lesions and RT-PCR of EM primary cell cultures.

Material/Methods: The expression of Twist and N-cadherin was analyzed by IHC in 38 EM lesions. Using RT-PCR, 7 EM primary cell cultures were analyzed for twist and N-cadherin.

Result: 7 primary cell cultures showed Twist and N-cadherin expression in the RT-PCR. Twist staining was detected immunohistochemically in 100% of the rectovaginal and peritoneal foci as well as in the ovarian EM. Twist staining was seen in 60% of adenomyosis uteri. N-cadherin was detected in 100% of sections of peritoneal, ovarian EM and adenomyosis, and in 89% of rectovaginal lesions.

Conclusion: The detection of Twist and N-cadherin offers a possible explanation for the invasive growth and metastatic potency of EM lesions. The regression of E-cadherin in EM tissue, which has been demonstrated in other studies and in which Twist may also be involved, is consistent with this. It is conceivable that the targeted regulation of the transcription factor Twist could contribute to a new therapeutic approach to inhibit metastatic growth and thus to improve the prognosis of malignant diseases, but also of EM.