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The results of four randomized international multicentric trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER2-neu positive primary breast cancer have been reported. These reports showed that even after short term follow up one year of Herceptin resulted in improved disease free, metastases free and overall survival. Design and results of these four studies and the recommendations of national and international societies for the use of Herceptin in the adjuvant setting will be discussed.

Purpose: Despite intensive research and surveillance up to now one has failed to reduce cerebral handicaps in newborn. Fetal heart rate tracing (CTG) and Doppler have reduced the number of subpartal severe asphyxia and fetal death. But, 90% of cerebral damage is a result of antepartal problems. Thus only 10% can be avoided by intensive surveillance during labor. Detection of antenatal cerebral injury is a rare case and its impact on later fetal life can only be estimated. Insight in fetal neuronal function is not possible. Factors and time pattern determining fetal cerebral injury are thus not known. This publication explains a new system with whom one might be able to get more insight in cerebral wellbeing during the fetal intrauterine life., Methods and Results: A new diagnostic approach is set up by recording fetal magnet encephalographic signals (fMEG) thus offering the opportunity to detect fetal brain function. An array which was especially designed to fit to the pregnant body consists of 151 sensors which are able to record the fMEG. Clinical testing is performed in the moment at the UAMS in Little Rock, Arkansas in Cooperation with the Institutes for Medical Psychology and the Frauenklinik in Tiibingen. First results and arising questions are published., Conclusion: With this new system a deeper insight into the fetal neuronal development and fetal wellbeing during pregnancy might be achieved thus reforming the fetal surveillance in the 21st century.

A number of genetic alterations are required for malignant transformation. However, these mutations provide the source for tumor-associated antigens which can be recognized by cellular effectors of the immune system. Recent advances in tumor immunology - such as the improved understanding of antigen presentation as well as T cell activation - have opened new perspectives for cancer immunotherapy. The advantage of using tumor cell based vaccines is that these comprise the complete antigen pool of an individual tumor for activating polyclonal immune responses. However, the induction of antigen-specific immune responses is impaired by the fact that T cell activation is depending on additional nonspecific costimulatory signals provided by the antigen-presenting cell. The majority of solid human tumors does not express costimulatory molecules and is unable to deliver all signals required for T cell activation. In contrast, tumors often induce immunologic tolerance. Therefore, the introduction of genes encoding costimulatory molecules such as CD80 or cytokines is aimed at conferring the immunostimulatory potential of tumor cells. We have undertaken efforts at endowing a breast carcinoma cell line expressing at least seven known tumor associated antigens with immunostimulatory competence by CD80 gene transfer. In preclinical studies this cell line was demonstrated to induce specific immune responses. We designed a phase I/II trial to administer the CD80-modified cell line to patients with metastatic breast cancer to determine the toxicities of the vaccination protocol and nature of the vaccine-induced immune response.

Objectives: Tibolone, a synthetic norethynodrel derivative, is effective at alleviating climacteric complaints and for osteoporosis prophylaxis. Concerning the cardiovascular system little data are available on possible direct effects on the vasculature compared with hormone replacement therapy. Since tibolone is pharmacologically best comparable to an estradiol/norethisterone combination (E2/NET), the aim of the present study was to compare these treatment regimens with respect to their effects on human vascular cells, this being the first study to investigate this question. -, Material and Methods: Human female coronary arteries were used, the most appropriate vessels for our issue in question. The experiments were conducted with endothelial cells as well as smooth muscle cells. Tibolone and E2/NET were tested at the concentrations 0.1, 1 und 10 microM. Incubation time was 24 h for endothelial cell cultures and 7 days for smooth muscle cell cultures. The effects on markers of pathophysiologically different problems were studied in a comparable manner: Markers of endothelial function such as prostacyclin, endothelin and plasminogen-activator-inhibitor-1 (PAI-1), markers of plaque initiation such as the adhesion molecules E-Selectin, ICAM-1 and the monocyte attraction protein-1 (MCP-1) and markers of plaque stability such as the precursor of the matrix-metalloproteinase-1 (pro-MMP-1). -, Results: Tibolone reduced the synthesis of endothelin as well as the concentrations of E-Selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers varied and was in the range of 11-42 %. similar inhibitions were seen for E2/NET; yet a significantly stronger inhibitory effect was found for pro-MMP-1. Moreover, E2/NET also reduced concentrations of ICAM-1 and MCP-1. Concerning smooth muscle cells only E2/NET was able to elicit an anti-proliferative effect. -, Conclusions: Tibolone can positively influence the synthesis of markers in cell cultures of human female coronary artery which modulate vascular tone and which play a decisive role in the various stages of atherosclerosis. In this respect estradiol combined with norethisterone is as potent as tibolone, in addition this combination is partially more effective and able to influence a wider range of markers which are important in the early stages of atherogenesis or for the stability of atherosclerotic plaques. Experimental studies such as the present one are useful to explore mechanisms, but clearly cannot replace clinical studies.

Objective: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions., Material and Methods: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions., Results: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically., Conclusion: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

Objective: In order to assess the efficacy and tolerability of leuprorelin acetate depot in pre-operative flattening of the endometrium prior to hysteroscopic endometrial ablation, 94 patients from eight centres were included in the per protocol analysis., Material and Patients: The patients included were pre- or peri-menopausal, had completed their family planning and had intractable uterine bleeding. The primary target criterion was the reduction in maximum endometrial thickness after two injections of leuprorelin acetate depot with an interval of four weeks between injections. Surgery took place two weeks after the second injection., Results: Sufficient pre-treatment was achieved in 91.5% of the patients with > 50% decrease and/or a type 1 endometrium according to sonographic and/or endometrial atrophy (Score 11) according to the central histological evaluation. The endometrium was flattened by a mean of 4.0 +/- 4.1 mm. In terms of clinical response, amenorrhoea, hypomenorrhoea or normal menstruation were achieved after endometrial ablation. Hence 91.5% of patients benefited from the overall treatment after six weeks and still 83% after six months. The trial medication was well tolerated overall. The most common side-effect described was hot flushes which could be attributed to the deliberate oestrogen withdrawal., Conclusion: In view of the good study results, hormone-suppressive pretreatment of the endometrium can be recommended prior to elective ablation. Surgery should take place during the oestrogen-suppressed phase.

The assessment of the activity of endometriosis provides a challenge during endoscopic procedures. Novel approaches can be developed in future based on more detailed understanding of the mechanisms of the pathogenesis of endometriosis. Angiogenic factors of local immunoreactions are important agents in the development and progression of the disease. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability and of the mitogenesis of endothelial cells. In endometriotic and endometrial tissues VEGF isoforms VEGF121, VEGF165, VEGF189 and VEGF206 are expressed. The amount of VEGF isoforms in the endometrium is regulated depending on the menstrual cycle. Macrophage recruitment by ectopic endometrial implants is an early step in the cascade of implantation and local peritoneal reaction. RANTES (Regulated upon Activation, normal T-cell-Expressed and Secreted) is a specific chemoattractant for monocytes and activated T-cells. Soluble products of activated macrophages play an important role in endometriosis associated infertility. The factors involved in angiogenesis and immune response are potential parameters to determine the activity of endometriotic implants and novel approaches for the treatment of endometriosis.

Anti-idiotypic antibodies, which imitate a tumor-associated antigen by their variable region, offer an elegant method for the induction of a specific immune response, when used as a surrogate antigen for immunization. We generated anti-idiotypic antibodies imitating 2 different tumor-associated antigens. I. CA125 for ovarian carcinomas and II. 14C5, a tumor-associated cell substrate adhesion molecule on breast cancer cells, whereas the first approach could be introduced in a first clinical trial and the second was evaluated in an immunocompetent animal model. For the induction of an immune response against CA125, 18 patients with advanced ovarian cancer (n = 6) or heavily pretreated recurrences (n = 12) were immunized with the anti-idiotypic antibody MAb ACA125. Patients were treated with 2 mg anti-idiotype antibody every two weeks for 4 injections i.m. and then monthly. 12 of 18 patients demonstrated an anti-anti-idiotypic (Ab3) response, which was to a lower extent also directed against CA125 and 9 of 18 patients developed a CA125 specific cellular immune response by their peripheral blood lymphocytes. Based on this data a follow-up clinical trial in advanced ovarian cancer patients with minimal residual disease in an adjuvant approach after primary therapy was started to evaluate the effect of the immune response on the progression free survival. For immunotherapy of breast cancer, we generated a murine monoclonal anti-idiotypic antibody (MAb ACA14C5), which imitates a cell substrate adhesion molecule on breast cancer cells. The anti-idiotype was introduced in an immunocompetent animal to prove his capability on induction of an immune and tumor response. The results showed a highly significant difference in the tumor growth of the ACA14C5 treated group in contrast to the controls starting the immunization on day 6 after tumor cell application with 10 of 12 animals being cured from their tumor burden. Prophylactic immunization against the invasion antigen of breast cancer by anti-idiotypic antibodies showed protection against increasing tumor burden. However, in the situation of established tumors only minor responses could be detected. Vaccination with anti-idiotypic antibodies comprises an effective method for induction of a specific immune response against non-immunogenic tumor-associated antigens and should be therefore considered in immunological approaches to tumor therapy, where the primary structure and sequence of the antigen, e.g. CA125, is up to now not available.

Objective: Long-term results after different types of operations for urinary stress incontinence (minimum follow-up: 18 months) as well as multiple risk factors for the pelvic floor were analysed in a retrospective study., Study Design: Between 1980 and 1992 1283 patients underwent surgery because of urinary stress incontinence at the University Women's Hospital in Heidelberg. The data of 478 patients, 430 of these after primary and 48 after recurrent surgery, were evaluated by questionnaires with regard to the long-term-results., Results: 57% of patients after primary surgical therapy and 37% after recurrent surgery were cured for longer than 5 years or since the operation. A cure or improvement of the incontinence could be observed in 80% after primary and in 73% after recurrent surgery. Among the vaginal approaches for primary surgery the hysterectomy combined with colporrhaphy was most successful (60% cured or more than 5 years continent, 80.5% at least improved). The Burch colposuspension revealed even better results among the abdominal approaches (64% cured or longer than 5 years continent, 86% at least improved) compared to the Marshall-Marchetti-Krantz procedure with a cure rate of 33%. For therapy of the recurrent urinary incontinence the abdominal Burch colposuspension showed the best results with cure rates of 50% and cure or improvement in 75%. Therefore the abdominal approach seems to be superior to vaginal techniques such as sling operations (33% cure rate, 67% at least improved) or only re-colporrhaphy (27% cure rate, 78% at least improved)., Conclusion: For primary incontinence the hysterectomy with vaginal repair or the Burch colposuspension have proved to be most successful. For recurrent urinary incontinence the abdominal colposuspension (Burch procedure) seems to be superior to other approaches.

We report on a patient with metastatic breast cancer confined to visceral (lung and pleura) site. A high-dose chemotherapy with peripheral progenitor blood cell transplantation was indicated. In contrast to other 24 patients two induction cycle chemotherapies (intensive dosis of Epirubicin/Ifosfamid/GCSF) didn't show any remission of metastases. Therefore a high dose chemotherapy with peripheral progenitor blood cell transplantation was not indicated any more. This patient had lung and pleura metastases and showed a complete remission after the following conventional chemotherapy (Carboplatin/Toxol) persisting more than 7 months. Non-responder after induction therapies have a poor prognosis but salvage therapy may be successful anyway. Mammary neoplasms can be sensible on special chemotherapy drugs only.

Objective: The long-term results following different types of operations for urinary stress incontinence (minimum follow-up: 18 months) as well as multiple risk factors for the pelvic floor with regard to the results of surgery are reviewed in a retrospective study., Study Design: Between 1980 and 1992 1283 patients underwent surgery because of urinary stress incontinence with or at the University Women's' Hospital in Heidelberg. The data of 478 patients, 430 of those following primary surgery and 48 following recurrent surgery, were evaluated from questionnaires with regard to their risk profile and long-term results., Results: 57% of patients following primary surgical therapy and 37% following recurrent surgery were cured for longer than 5 years or since the operation. A cure or improvement of the incontinence could be observed in 80% following primary and in 73% following recurrent surgery. Long-term results were significantly unfavorable, if the patient was exposed to one or several of the following risk factors: 1. Strain at work by carrying weights more than 5 kg 2. At least medium-hard housework, psychological tensions in the private sphere or idle women, who take a car for shopping 3. Double strain with at least medium-high burden with house-work and physical strain at work, Conclusion: Long-term results following primary urinary stress incontinence surgery are influenced by certain risk-factors.

Paraneoplastic retinopathies are rare paraneoplastic phenomena resulting in retinal degeneration. They occur in association with different tumor types, yet most frequently encountered in small cell carcinoma of the lung. Clinical symptoms may be present before the diagnosis of the underlying malignancy. They are characterized clinically by progressive visual loss with ring scotomas, photopsia and night-blindness. An autoimmune disorder is suggested. In the sera of patients antiretinal antibodies may be detected that are sometimes reactive with the 23 kD retinal antigen recoverin, a photoreceptorprotein. We report on two patients with breast cancer who developed paraneoplastic retinopathy during the course of disease. Immunologic tests showed antiretinal antibodies that were not reactive with the 23 kD retinal antigen recoverin.

To establish the requirements for real-time transfer of an ultrasound examination via telecommunication network the following tests were performed: The ultrasound data were transferred from the video out of an ultrasound system to a basis terminal of the German Telekom. Simultaneously, an external video camera filmed the positioning and movements of the ultrasound transducer, and the verbal comments were recorded. These informations were transmitted to Karlsruhe and London, where they were rerouted to the examination room in Heidelberg. Here the informations were received on a Telecom reception unit/terminal and compared directly with the initial signal. The quality was sufficient if the moving ultrasound images and the camera image of the transducer as well as the oral comment were transmitted over 2 parallel ISDN lines. The delay to a real-time transmission of the examination process is only in the range of milliseconds. If only one ISDN line is used, the image quality is unsatisfactory, three parallel lines do not bring significant improvement of image quality. Telemedicine seems a new possibility to bring the knowledge of specialized centers to the practicing gynaecologists thus avoiding unnecessary referrals. Still unanswered, however, are the problem of liability, data protection and costs.

Both pre-operative transvaginal sonography and laparoscopical diagnosis leave gaps in the diagnosis of adnexal tumors. The combination of both methods seems to fill these gaps. For diagnosis with Laparoscopical Sonography a special scan head is needed: After removing the optical components there was a little linear-array installed into the original gastroscope with a diameter of only 9 mm which enables maximum flexibility during examinations. The linear-array consists of 128 crystals with a frequency of 7.5 MHz (penetration depth: 6 cm), enabling B-Image Sonography, Pulsed and Color Doppler as well as Angio-Color-Technique. Laparoscopical Sonography in addition to transvaginal and transabdominal sonography leads to progress in diagnosis and therapy. As the scan head can be placed directly in front of the area which is normally hardly detectable diagnosis is possible and plannings for the further operations as well as color-doppler controls during operations can be improved. In several cases this method allowed detection of metastases of the liver which were not visible by transabdominal ultrasound.

The present study reports first experiences with falloposcopy for extended diagnosis in tubal sterility. In a total of 38 patients, n = 62 tubes were to be examined falloposcopically. Catheterization was successful in 85.5%. After successful catheterization, optically interpretable images were obtained in 93.6%. The overall success rate was therefore 80%. Considering the anatomical segments of the tube, no differences were found neither for catheterization nor for visualization. The spectrum of intratubal findings extended from normal in 25% to partly obstructive, nodular or non-nodular pictures, together with various degrees of mucosal alteration with or without synechia formation.

In an overall study population (3 different study designs) of n = 285 patients the role of laparoscopic resp. laser-assisted techniques was evaluated on the basis of the results of distal tubal reconstruction. An interventional comparison of a laparoscopic (n = 150) with a retrospective microsurgical (n = 135) group of patients with distal tubal pathology showed a significantly higher baby-take-home rate in the laparoscopically treated patients (38% vs. 22.2%, p < 0.05), but detailed critical analysis of indication revealed a certain selection effect in the laparoscopic group. A prospective study on laser (n = 100) and non-laser techniques for salpingostomy showed in no significant differences between the two groups, as results were concerned (delivery 35% in the laser, 44% in the non-laser cohort). In a prospective randomized subgroup laparoscopic fimbrial eversion with the laser was compared to suture eversion (n = 20). In both groups the reocclusion rate was of 20%. On may thus conclude, that the most important surgical approaches for treatment of a tuboperitoneal sterility: micro-surgery and endoscopy, resp. the various surgical techniques: laser and non-laser, should not be regarded as competing procedures, but as components of a multimodal strategy. The indication, however, must be critically viewed in every particular case. Of major importance being strict scientific evaluation criteria to prevent misinterpretations, e.g. based on indication-specific selection.

Based on technical and clinical application research a new generation of so-called micro-endoscopes was developed, with a wide range of indications in gynaecology as well. The innovative potential of these new endoscopes is, however, still to be considered against the background of the risks of erroneous findings at laparoscopical and hysteroscopical diagnosis, so that here too, clear indications will have to be worked out.

This paper reports on an open explorative study on the absorption of the electrolytfree distension medium Purisole (Mannitol-Sorbitol solution) during hysteroscopic procedures and its effects on laboratory and cardiovascular parameters. Intra- and postoperative levels of mannitol and sorbitol in urine were also measured to determine elimination of both components. The study population consisted of 84 patients aged 22-62 years. 54 women underwent ablative (resection of submucous fibroids, endometrial ablation, septum resection), 30 patients non-ablative operative hysteroscopic procedures (synechiolysis, hysteroscopic proximal tubal catheterisation). The duration of operations was between 23-48 minutes. Ethanol was added to the Purisole solution for determination of resorption. In 57 cases 1% ethanol in Purisole was used as irrigating fluid. In 27 cases 2% ethanol was added to the distension fluid. A median slight encrease of central venous pressure was noted during the procedures. 18 women had an intraoperative hyponatriaemia (only 4 patients < 130 mmmol/1). For the 15 patients, in which ethanol absorption was noted, fluid resorption was calculated on the basis of blood alcohol concentration (median 850 ml). Resorption was below the determination threshold in the other 69 women. Urine examination showed intra- and postoperatively increased concentrations of sorbitol and mannitol. Fluid overload and intraoperative cardiovascular complications did not occur in our patients.

Whereas 65-70% of ovarian malignancies are of the epithelial type, the occurrence rate of stromal tumors is of approx. 7% and that of germ cell tumors of approx. 15%. Stromal tumors are mostly of the granulosa cell type, whereas germ cell tumors occur mainly as dysgerminoma (occurrence 0.9-2%), endodermal sinus tumors, or teratoma. Organ preservation is discussed in relation to the characteristics of these special tumor types. Granulosa cell tumors, representing 70% of the tumors of the gonadal stroma, occur unilaterally in approx. 97% of cases. 10-year-survival in stage I is over 90%. In stages II and III a complete remission after chemotherapy (acc. to the PVB, VAC, or BEP protocol) may be achieved in approx. 60% of cases. Due to these characteristics organ preservation seems feasible. Since dysgerminoma represent the most common malignant germ cell tumor in children, adolescents and pregnant women (up to 17% of all dysgerminoma are diagnosed during pregnancy), the wish for organ preservation is the more understandable. However, bilaterality, occurring in 20% of cases, has to be considered. Especially in large tumors lymphatic metastases also have to be taken into account. In cases of endodermal sinus tumors and teratoma, overall survival, mainly in patients with advanced disease, depends on the response to an aggressive chemotherapy. Preconditions for organ preservation are the patients' urgent childbearing desire, their information concerning the 5-7% risk of recurrence, an adequate oncologic postoperative care and optimally, after delivery, removal of the contralateral ovary and re-staging. The operative procedure requires removal of the corresponding adnexa, wedge dissection of the contralateral ovary, omentectomy, and depending on the histological tumor type a pelvic, possibly paraaortal lymph node dissection. No generally accepted standards are available for organ preserving surgery of stromal tumors, especially of the granulosa cell type. Prognosis is essentially influenced by a possible rupture being present, tumor size, cellular atypia, and the mitotic index. If one takes into consideration the possibility of lymph node metastases, at least a pelvic lymph node dissection should be recommended. In cases of metastases additionally a chemotherapy (VAC protocol) is indicated. Among germ cell tumors, dysgerminoma and non-dysgerminoma are treated differently. Non-dysgerminoma are endodermal sinus tumors, teratoma, embryonal carcinoma and mixed forms. For both groups operative management may aim at tumor reduction and in principle organ preservation. Whereas for dysgerminoma an adjuvant radiation therapy is feasible, in cases of non-dysgerminoma the response to a chemotherapy is the only factor influencing prognosis. Chemotherapy as adjuvant treatment is not indicated for pure dysgerminoma stage Ia, and pure solid teratoma stage Ia Gl. For all other dysgerminoma adjuvant chemotherapy, VAC protocol, and chemotherapy according the the BEP protocol for non-dysgerminoma is recommended. In cases of metastatic spread, in both groups an aggressive chemotherapy (BEP protocol) is most commonly performed.

Angiogenesis is an essential condition for tumor growth. Therefore, it seems to be of interest to prove if blood flow and vascularization of breast tumors give information concerning their dignity. Consequently, 205 patients with palpable and/or mammographically detected breast tumors were examined prior to surgery by doppler sonography for blood flow in the area of the tumor. In 174 patients of this group the corresponding area of the contralateral breast was also screened by doppler ultrasound. With third doppler generation angiodynography tumors can be visualized as B-images with simultaneous information on vascularization. An integrated doppler system shows the detected blood flow in form of a doppler curve, also allowing quantification according to doppler criteria (Resistance Index RI). Blood flow detection in the tumor itself was successful in 71% of all malignancies, whereas in only 6.6% of the 76 benign lesions (n = 5) blood flow was found in the central tumor area. In the area surrounding the tumor blood flow was detected in 83% of all carcinomas, but only in 29% of benign findings. Blood flow could be detected significantly higher in malignancies than in benign lesions (p = 0.003). Blood flow detection in the tumor itself was a highly specific (93%) method of discrimination between malignant and benign breast tumors. Further quantification by means of doppler parameters only increases insignificantly specificity, quantification of blood flow in the area surrounding the tumor using the RI and the comparison with the contralateral breast could improve the diagnostic value as our findings RI < 8 for benign vs. > or = 8 for malignant lesions demonstrated. Detection of malignant tumors showed a sensitivity of 80%, a specificity of 90%, and a positive predictive value of 93%. In patients with breast cancer (histologically confirmed) the detection rate of blood flow in tumors and surrounding areas was independent of tumor size or nodal status.

Though abdominal colposuspension is an established operative procedure in the therapeutic spectrum of female urinary stress incontinence, there is controversy concerning new access routes and fixation techniques. On the basis of a comparison between results of a "feasibility" study at our department concerning the trans- and extra-peritoneal endoscopic access as well as suspension techniques with alloplastic material and suturing vs. stapler application, and al literature survey, a synoptic concept is being evaluated. In case of critically made indication, first trends show that results of laparoscopically and retziusscopically assisted techniques are comparable to those of conventional procedures. However, the lack of long-term results as well as an initially prolonged operation time have to be considered. In the meantime an extraperitoneal transumbilical colposuspension was attempted in 2 patients, already unsuccessfully operated upon (conventional Burch) previously. Due to extensive perivesical adhesions a laparotomy had to be performed. The limits of the endoscopic approach seen to be reached in these cases.

Ovarian tumors during pregnancy are a rare event. In most cases the tumors are detected accidentially during routine examination, ultrasound or a caesarean section at term. The incidence of malignant ovarian tumors is about 1:10,000 to 1:40,000 pregnancies. Histologic subtypes and prognosis do not differ from tumors not associated with pregnancy, it seems however, that there are more lesions of borderline malignancy and of low grade. Therapy depends mostly on the age of gestation and tumor stage. Conservative surgery is recommended only in stage IA disease. Radical surgery and if necessary adjuvant therapy is recommended during the first trimester. In the third trimester a caesarean section can be followed by radical surgery, provided that there is a close cooperation between gynecologists and pediatricians. In the second trimester this regimen is possible only as an exception which includes a critical maternal risk-benefit assessment.

Endoscopic ovarian surgery is currently spreading tremendously, but also rather uncritically. The technical possibilities both of organ preserving and ablative endoscopic surgery are controversial, so that structuring of the indication for an endoscopic procedure as well as optimization of the endoscopic removal of ovarian tumor or adnexae is of utmost relevance. Therefore, a study was performed at the Department of Obstetrics and Gynaecology of the Heidelberg University with the following aims: Risk evaluation of operating into an ovarian malignancy at endoscopy for "presumably" benign cystic ovarian tumors in n = 100 cases in Heidelberg and literature survey Analysis of problems and complications during clinical application of laparoscopic lap sacs for removal of cystic adnexal tumors or adnexae (n = 50) Experimental examination of the risk of an endoscopic lap sacs to rupture during a procedure The risk of endoscopically operating into an ovarian cancer lies between 0.4 and 3% according to literature data. Despite maximal preoperative selection, mainly by ultrasound examination, in our group of 100 patients, in three women without preoperative signs of malignancy but with discreet intracystic structures in the ultrasound, an endoscopic adnexectomy with complete removal in a lap sac was performed, and though immediate section for microscopic examination was negative, final histology revealed one ovarian cancer la and 2 borderline tumors, same stage. In the time period analyzed, three further patients were referred to our center for secondary, delayed (median 3 months) staging after endoscopic procedures for presumed benign lesions. Clinical application of lap sacs proved the necessity of an intensive training. In 3 patients an intraperitoneal rupture of the sac occurred. Typical problems were volume discrepancies between sac respectively abdominal incision and tissue to be removed (28% of cases). The risk of rupture of the various lap sacs examined differed significantly (p < 0.05). Due to the complex pathological nature of cystic adnexal tumors, a 100% selection for the endoscopic approach is not feasible. Therefore, an endoscopic procedure should only be performed after optimal preoperative diagnosis and, in case of the slightest doubt, only if intraoperative microscopic examination is available, and the possibility to perform an immediate staging laparotomy. Sufficient information of the patient is relevant. Laparoscopic removal of tumor or adnexae should be performed in a lap sac. However, there is no absolute certainty of preventing spillage even with the lap sac, since not all endoscopic sacs available are of a sufficient quality.

According to recent reports, the microendoscopic lactiferous duct investigation (ductoscopy) could improve diagnosis in case of pathological nipple discharge. However, the description of a reproducible and reliable methodology, suitable for thorough evaluation of the lactiferous duct is missing so far. Therefore, the pressure study developed a procedure, that may serve now as an experimental basis for further clinical evaluation. Access to the mamillary duct is primarily gained using atraumatic flexible teflon catheters. Corresponding to the diameter of the duct, either a semirigid 0.87 mm fiberendoscope can be successfully introduced via a 1.2 mm catheter, or a flexible 0.50 mm fiberendoscope via a 1.0 mm catheter. A controlled distension using few milliliters of ringer's lactate is the prerequisite for clear visualization of the intraductal space and protection against iatrogenic wall lesions. Metal microtocars are available as prototypes. They carry a somewhat higher risk to perforate, but are advantageous when pointing at an intraductal structure and using the microtrocar as a mark for microdochectomy.

We report about a case of a highly intracervical located microcarcinoma of the cervix uteri, which could solely be diagnosed by a sufficient sampling technique using cyto-brush. The same case could not be diagnosed without the presence of endocervical cells in the endocervical smear either.

A hysteroscopic endometrial ablation (HEA) under maximal anesthesiologic surveillance was performed on 34 high-risk patients (group I: chronic anticoagulant therapy n = 26; group II: endogenous coagulopathy n = 8) with therapy resistant meno-metrorrhagia to avoid a hysterectomy (HE). Total amenorrhea, or a least hypomenorrhea respectively cyclic spotting could be attained primarily in 22 patients (group I: 19; group II: 3), after a repeat procedure in further 6 patients (4 in group I, 2 in group II). Subjective evaluation of surgical results (overall 22 patients primarily satisfied, 6 secondarily) also differed between the two subgroups (group I: p < 0.01 primarily satisfied; p < 0.05 secondarily satisfied vs. p < 0.05 and p < 0.01 in group II). A HE had to be performed on two patients due to extensive adenomyosis uteri interna (group II). The significantly better results in the anticoagulation group were probably due to the basic illness. Larger groups will, however, be necessary before any conclusions from this difference can be drawn. No surgical or anesthesiological complications occurred. There also were no major postoperative complications (1 endomyometritis, 2 cervical stenoses). Endometrial ablation was found to be a valuable treatment alternative for this specific group of patients with severe coagulopathy, thrombo-embolic or thrombotic disease.

To date, the therapy of first choice in case of proximal tubal pathology is resection of the occluded segment and microsurgical reconstruction. Essential disadvantage of this rather successful method consists in the need of a laparotomy. According to the concept of minimal invasiveness a pilot study has been undertaken to evaluate hysteroscopic proximal tube catheterization (HPTC) and balloon dilatation for recanalization. This attempt has proven intraoperatively successful in more than 80% of the cases and the first pregnancy and birth following HPTC can yet be reported.

To date the tremendous spread of operative laparoscopic procedures associated with monopolar high-frequency techniques has lead to an increase in complications caused by monopolar leakage currents. Experimental-surgical measurements on minipigs have shown no significant leakage currents in clinical relevant power range during laparoscopic application of a bipolar needle electrode as compared to monopolar electrodes. Practicability and safety of the bipolar electrode was proven in 100 operative laparoscopies for organ preserving or reconstructive surgery. In summary, with the new laparoscopic bipolar needle electrode a secure surgical instrument is available, with which finest tissue handling and minimal thermal damage feasible.

The availability of adequate endoscopic instruments has led to an increased interest in hysteroscopic surgical procedures. An electrolyte-free irrigation fluid is essential for the distention of the uterine cavity, with acceptable uterine distention occurring at 80-150 mmHg. The HSK syndrome, the intravascular absorption of a hypotonic irrigation fluid with subsequent hypotonic hyperhydration with hyponatremia, has to be considered as a risk during hysteroscopic procedures. Analogous to the TUR syndrome, intravasation occurs through the vascular spaces opened during large ablative surgical procedures resulting in the absorption of the fluid used for irrigation. Occasionally, a tear in the lower uterine segment from dilation or perforation of the uterus may expose large vascular channels. Outflow through the tubes is not a significant factor. Continuous CVP measurement allows the detection of intravascular absorption of the irrigation fluid and may be included in the routine monitoring for these procedures. The duration of the hysteroscopic procedure should be limited to 60 min. Addition of ethanol to the irrigating fluid may be suitable for early detection of fluid absorption. However, commercial solutions are not yet available.

Hysteroscopy has become an integral part of the overall gynaecological surgical concept. On the one hand the experience of our study group as well as a literature survey have demonstrated that results of hysteroscopic metroplasty, resection of submucous myoma and synechiolysis are at least comparable to those of conventional procedures, the advantages of minimal invasive surgery being evident. However, increasing complications, even with a lethal outcome, due to deficient technical equipment or insufficient training of the surgeon are reported. Yet, a survey of complications in literature and in our own series of hysteroscopies (n = 200), shows a median complication rate below 1%. Knowledge of possible complications, symptoms and management alternatives is, however, a first requirement for application of these minimal access procedures. The second major precondition being a well structured training program for surgeon and assisting team. With the recently developed in-vitro-simulation trainer, the HysteroTrainer, training of the entire spectrum of hysteroscopic procedures, including laser and high frequency electrosurgical applications, is now feasible. The simulator may also be employed for security checking of the complex hysteroscopic equipment.