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Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Von der Deutschen Krebshilfe im Rahmen des Leitlinienprogramms Onkologie gefordert fanden sich unter der Federfuhrung der Deutschen Gesellschaft fur Gynakologie und Geburtshilfe und der Arbeitsgemeinschaft Gynakologische Onkologie in der Deutschen Krebsgesellschaft Mandatstrager von 34 Fachgesellschaften, Patientenvertreterinnen sowie 6 Experten zusammen. Der folgende Artikel skizziert die wichtigsten Ergebnisse der 4‑jahrigen Arbeit.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.

Im April 2018 erschien die erste deutsche interdisziplinare S3-Leitlinie fur die Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom. Dieser Beitrag ist die Zusammenfassung des Kap. 4: „Diagnose, Fruherkennung, Bildgebung und Pathologie“ mit dem Ziel, dem Leser eine Kurzfassung an die Hand zu geben. Dargestellt sind die Empfehlungen zur Diagnose und Fruherkennung von Endometriumkarzinomen, ferner die Indikationen zur Bildergebung und die Anforderungen fur die pathologische Aufarbeitung.

Mit 11.000 Neuerkrankungen in Deutschland ist das Endometriumkarzinom das vierthaufigste Malignom der Frau. Ein guter Algorithmus in der Diagnostik hat einen besonderer Stellwert im Hinblick auf gute Vorbereitung und Planung der operativen Versorgung sowie in der Vermeidung unnotiger operativer Eingriffe. Dazu tragen auch die seit 2010 geltenden Modifikationen der Stadieneinteilung bei. Die Ubersichtsarbeit erfolgte auf der Basis einer selektiven Literaturrecherche. Postmenopausale und azyklische Blutungen mit oder ohne Vorliegen von Risikofaktoren sollten histopathologisch abgeklart werden. Fur ein Screening asymptomatischer Patientinnen gibt es derzeit kein sinnvolles Verfahren. Die diagnostische Hysteroskopie mit fraktionierter Abrasio stellt den Goldstandard in der Diagnostik dar. Verfahren zur Festlegung der Invasionstiefe leiden unter ihrer schlechten Sensitivitat und sind derzeit nicht Bestandteil der praoperativen Routine. Die Klassifikation des Endometriumkarzinoms ergibt sich gemas dem chirurgisch-operativ erhobenen Befund. Die aktuellen Modifikationen fuhren zu einer besseren Einteilung und ermoglichen eine sinnvollere Zuordnung zu einzelnen Therapieoptionen. Die Schnittbildverfahren zeichnen sich durch eine sehr gute Spezifitat aus, zeigen aber durchweg eine schwache Sensitivitat.

Die Lymphknotenoperation gehort zum etablierten Standard der Karzinomchirurgie auch in gynakologischen Onkologie. Bereits seit einigen Jahren wird jedoch intensiv diskutiert, in welchem Umfang dieses Vorgehen noch zeitgemas ist [1], insbesondere im Hinblick auf den therapeutischen Effekt jenseits der Informationen zur Tumorausbreitung. Die vorliegende Ubersicht fasst den derzeitigen Stand zur Lymphadenektomie fur die gynakologische Onkologie zusammen.

Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patientʼs quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.

In 2013, 2009 and 2006, the Arbeitsgemeinschaft Gynakologische Onkologie evaluated the therapeutic approaches for endometrial carcinoma and the adherence to their guideline in Germany. Here, the adjuvant treatment decisions were presented. A questionnaire was developed and sent to all 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006, respectively). The results of the questionnaires were compared with the recommendations of the guideline and with each other using Fisher’s exact test. Responses were available in 40.0 % in 2013, 33.3 % in 2009 and 35.8 % in 2006. Participants recommended external beam radiotherapy (EBRT) in 13 out of 16 requested stages and vaginal brachytherapy (VBT) in only 10 out of 16 requested stages as suggested by the guideline. Comparing the results of 2013 with 2009, less participants used EBRT and VBT in 7 out of 16 and in 6 out of 16 requested stages, respectively. Conversely, more participants offered adjuvant chemotherapy (CT) in 2013 (90.4 %) compared to 61.9 % in 2009 (p

In 2013, 2009, and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated the therapeutic approaches and the adherence to their guidelines for endometrial carcinoma (EC) in Germany. Here, we present the results concerning the surgical procedures.A questionnaire was developed and sent to 682 German gynecological departments in 2013 (775 in 2009 and 500 in 2006). The results were compared with the recommendations of the guideline and with each other.Responses were available in 40.0 % in 2013, 33.3 % in 2009, and 35.8 % in 2006, respectively. Pelvic lymphadenectomy (LAN) was performed in accordance with the guidelines with some exceptions in 2013, 2009, and 2006, whereas paraaortic LAN was performed in accordance with the guideline only in 2009. Histological high-risk subtypes of EC received pelvic and paraaortic LAN in 2013, 2009, and 2006 in accordance with the guidelines with small exceptions. LAN for Patients, who were postoperatively upstaged or upgraded, was not conducted in accordance with the guidelines in 2013, 2009, and 2006. In 2013, 84.6 % of the participants offered the laparoscopic approach (LSA) for hysterectomy and bilateral salpingo-oophorectomy, 63.3 % for pelvic LAN, and 49.1 % for paraaortic LAN, respectively. More participants offered the LSA in 2013 compared to 2009 and 2006 (p values0.014).The paraaortic LAN, the LSA as well as the second operation on patients who had postoperatively been upstaged were not conducted in accordance with the guideline [CORRECTED]. Improvements concerning surgical treatment are possible and might lead to higher survival rates and a reduction of morbidity in patients with EC in Germany.

ObjectiveIn 2009 and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated therapeutic approaches for endometrial carcinoma (EC) in Germany.Methods and MaterialsA questionnaire was developed and sent to 775 German gynecologic departments in 2009 (500 in 2006). The results of the questionnaires were compared with each other and with the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie’s guideline. Subgroup analyses were performed, dividing the participating centers into small and large centers and into centers with less and more experience with EC.ResultsResponses were available in 33.3% in 2009 and 35.8% in 2006. Comparing 2009 with 2006, it became apparent that peritoneal washing cytology was performed in 94.6% versus 86.9% (P= 0.008), pelvic lymphadenectomy (LAN) in 98.3% versus 95.3%, and paraaortic LAN in 90.2% versus 73.8% (P< 0.001) for endometrioid EC, and LAN for histologic high-risk subtypes of EC in 99.6% versus 94.2% (P= 0.001), respectively. In 2009, all these criteria met the recommendation of the guidelines. Reoperation for LAN after postoperative upstaging was performed in 66.1% versus 50.6% (P= 0.002), and adjuvant systemic treatment with chemotherapy and endocrine therapy was performed in 63.7% versus 48.8% (P= 0.003) and 25.7% versus 15.4% (P= 0.014), respectively. This showed nonadherence to the guidelines. Laparoscopic approach was performed in 30.4% versus 19.7% (P= 0.014) of the participating centers, respectively. In subgroup analysis, laparoscopic approach showed a significant difference between small centers (11.5%) and large centers (27.3%) in 2006 (P= 0.012).ConclusionsGerman hospitals increasingly follow the guidelines concerning LAN and peritoneal washing cytology. However, recommendations concerning reoperating in upstaged patients and adjuvant treatment decisions do not meet the guidelines, thus underlining great uncertainties in this field of gynecologic oncology.

Objective P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer. Methods 40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann–Whitney test for two independent groups and the Fisher's exact test for dichotomous groupings. Results In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression. Conclusion Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.

Metastasis from primary tumors remains a major problem for tumor therapy. In the search for markers of metastasis and more effective therapies, the tumor metabolome is relevant because of its importance to the malignant phenotype and metastatic capacity of tumor cells. Altered choline metabolism is a hallmark of cancer. More specifically, a decreased glycerophosphocholine (GPC) to phosphocholine (PC) ratio was reported in breast, ovarian, and prostate cancers. Improved strategies to exploit this altered choline metabolism are therefore required. However, the critical enzyme cleaving GPC to produce choline, the initial step in the pathway controlling the GPC/PC ratio, remained unknown. In the present work, we have identified the enzyme, here named EDI3 (endometrial differential 3). Purified recombinant EDI3 protein cleaves GPC to form glycerol-3-phosphate and choline. Silencing EDI3 in MCF-7 cells decreased this enzymatic activity, increased the intracellular GPC/PC ratio, and decreased downstream lipid metabolites. Downregulating EDI3 activity inhibited cell migration via disruption of the PKCα signaling pathway, with stable overexpression of EDI3 showing the opposite effect. EDI3 was originally identified in our screening study comparing mRNA levels in metastasizing and nonmetastasizing endometrial carcinomas. Both Kaplan–Meier and multivariate analyses revealed a negative association between high EDI3 expression and relapse-free survival time in both endometrial ( P < 0.001) and ovarian ( P = 0.029) cancers. Overall, we have identified EDI3, a key enzyme controlling GPC and choline metabolism. Because inhibition of EDI3 activity corrects the GPC/PC ratio and decreases the migration capacity of tumor cells, it represents a possible target for therapeutic intervention.

The public discussion about health care financing has an enormous relevance for the field of gynaecology and obstetrics. This second part of the paper of the financing commission of the DGGG presents essential financial aspects and problems, influencing our speciality. Among other aspects, the inputs of the DRG system are discussed for our field. The representation of all levels of care and all German states in the InEK calculation system is still a problem. Regarding the inpatient care, the number of cases has decreased by 23 over the last years due to the shift to the outpatient setting. Surgeries in the outpatient setting have increased by 31.5 from the year 2004 to the year 2008 (all specialities). Moreover, a decrease of obstetric cases by 5.7 and cases directly associated with birth by 7.3 has to be mentioned. Altogether, our field has lost 6.8 of all inpatient cases over the last years. The economic pressure is still high and it is difficult to maintain cost recovery. Regarding the personal resources, legal demands are problematic for perinatal centres, e. g. loss of the on-call duty possibility, availability of medical specialist expertise and necessity of permanent standby service of the head of the perinatal centre. Further problems of the inpatient setting concern the field of urogynaecology (lack of young academics, new technical procedures with lack of data, missing representation of complex surgeries and lack of reimbursement in case of surgeries in the outpatient setting) and the benign and malign gynaecological surgery. While standard procedures are almost represented in the DRG system, there is still a high demand for development of appropriate reimbursement for complex and infrequent case constellations, interdisciplinary procedures and simultaneous multiplex surgeries. The collaboration of all colleagues is essential.

Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. Conclusion: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2–, ER-, and PR-negative tumors.

Background. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. Methods. Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. Results. Both uPA ( p =0.011) and PAI-1 ( p =0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p =0.021 for uPA and p =0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage ( p =0.003) and with histological grading ( p =0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. Conclusion. The combination of high cytosolic concentrations of uPA (>5 ng/mg total protein) and high PAI-1 (>20 ng/mg total protein) may reveal a group of patients with increased risk of progression.

Objective The results obtained using plastic surgery reconstruction in 207 patients with a primary or recurrent vulvar carcinoma were analyzed with regard to the surgical procedures applied, pre-treatment and post-operative findings, along with the long-term oncological disease course. Study design Standardized data concerning the surgical procedures applied and clinical factors were collected in a databank and statistically analyzed. Results The flaps employed were termed either ‘local' (cutaneous or fasciocutaneous; n =84) or ‘regional' (myocutaneous, n =123). For local flaps, the rate of secondary healing was 31%, dropping to 20% for regional flaps. Such healing disturbances often affected the donor region and did not lead to lasting clinical problems such as stenosis or distortion. Severe disturbances of wound healing (loss of more than 10%) were not observed in local flaps, whereas such problems were encountered in 5.9% of regional flaps. Gluteal thigh flaps were most frequently applied and were also the most successful type of myocutaneous reconstruction. Therapy was selected on an individual basis according to tumor status. Conclusion Plastic surgery reconstruction broadens the range of operative therapies available for the treatment of vulvar carcinomas, especially those at an advanced stage or recurrent tumors, and leads to a favorable oncological disease course as well as improved cosmetic results.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

PURPOSE This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results. METHODS All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods. RESULTS In 123 local (cutaneous or fasciocutaneous) and 84 regional (myocutaneous) flaps we found a primary healing in about 2/3 of the cases. Local flaps exhibited secondary healing in 31 %, regional flaps in 20 %. This often involved the donor sites and generally did not present any permanent problems. Pronounced healing disturbances (necrosis of more than 10 %) was not achieved in local flaps, in regional flaps it aroused in 5.9 %. Gluteal femoral flaps were used most frequently and showing the best results of all myocutaneous flaps. They were comparable with the local reconstructions by a high degree of reliability and healing. In 15 cases a tissue-loss was observed. In these patients, elevated risk factors, certain oncological characteristics and technical problems could be demonstrated. CONCLUSION Plastic surgery enlarges the spectrum of operative therapy of vulvar cancer, especially in extensive or recurrent tumors, leading to a favourable oncological outcome and good cosmetic results. Severe healing disturbances are rare and can be controlled.

Objective: To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs with respect to qualitative improvements of medical care before and after surgery. Methods: Between June 1993 and July 2003 129 women with cervical cancer were assessed before and 4 and 12 months after surgery by semistructured interviews and standardised questionnaires. Thanks to funding, since 1999 all patients with a diagnosis of genital or breast cancer can participate in this prospective study. In this paper we will focus on therapy-related changes in quality of life and body image in women with cervical cancer. The evaluation of quality of life (CARES) incorporated five aspects: physical and psychosocial health; marital and sexual status; medical interaction. With respect to body image (Strauss and Appelt) the attractiveness/self-confidence and sexual uncertainty were evaluated. Results: Before surgery, women with a Wertheim's procedure had significantly less problems with regard to the quality of life global score (p = 0.002) and several subscales compared to women with a pelvic exenteration. After surgery, both groups indicated that sexual problems were the greatest limitation in terms of quality of life, especially in women with non-reconstructive surgery as well as in women with adjuvant radio- and/or chemotherapy. With respect to body image, attractiveness/self-confidence was significantly reduced postoperatively compared to the preoperative status in both groups (p = 0.000), and also worsened with the extent of treatment. Conclusion: This on-going study demonstrates the interrelationship between the treatment and the patient's quality of life, especially with regard to sexuality and body image. Our results suggest not only providing reconstructive surgery if possible, but also integrating psychosocial information on future quality of life before surgery as well as offering psychosocial support related to the extent of treatment after surgery.

Fragestellung: Das geplante Mammographiescreening wird eine grosere Zahl unklarer Mammographiebefunde hervorrufen, in Zukunft wird daher die Zahl der Mammabiopsien zunehmen. Mit der stereotaktischen vakuum-assistierten Mammabiopsie steht ein Verfahren zur Verfugung, welches eine patientenschonende Moglichkeit der Abklarung verspricht. Ziel der vorliegenden Untersuchung war es, die klinischen Ergebnisse dieser Methode zu uberprufen.Material und Methode: 166 vakuum-assistierte Mammabiopsien wurden mit einem standardisierten Untersuchungsprotokoll durchgefuhrt und ausgewertet.Ergebnisse: Die histopathologische Aufarbeitung zeigte in 75,8 % gutartige Befunde. Lasionen mit Risikocharakter und nichtinvasive Neoplasien wurden in 18,6 % diagnostiziert, invasive Karzinome fanden sich bei 9 Biopsien (5,4 %). Die Komplikationsrate war insgesamt sehr gering. Weder Haut- noch Thoraxwandverletzungen, noch Schmerzhaftigkeit oder intraoperative Blutungen fuhrten zu einem Abbruch. Postinterventionell fanden sich vier Nachblutungen, im weiteren Verlauf in 28,3 % oberflachliche, in 3 % ausgedehnte Hauthamatome, alle ohne die Notwendigkeit einer operativen Revision. Des Weiteren sahen wir in keinem Fall eine Infektion. Im Durchschnitt wurden 17,2 (8-31) Gewebezylinder gewonnen. Nach Entnahme von 18 Zylindern stand in allen Fallen der endgultige histopathologische Befund fest, desgleichen war in allen Fallen der Mikrokalk getroffen. Die underestimation-rate betrug drei von funfunddreisig Fallen.Schlussfolgerungen: Die vorliegende klinische Studie zeigt, dass die stereotaktische Vakuumbiopsie ein sehr zuverlassiges Verfahren zur Abklarung unklarer Mammabefunde darstellt, welches deutlich geringere Komplikationsraten als eine konventionelle Biopsie aufweist. Objective: Screening mammography (as planned in germany) will lead to an increasing number of breast biopsies. The purpose of this study was to determine the promise of directional large core biopsy as a patient-protecting therapeutic method.Material and methods: 166 vacuum assisted, X-ray-guided biopsy procedures were analysed.Results: Histopathologic examination resulted in 75.8 % benign lesions. Atypical proliferation and noninvasive neoplasia was found in 18.6 %, invasive carcinoma in 5.4 % of the biopsies. Complications were few. Neither skin- or chestwall injuries, nor pain or intraoperative bleeding caused an abortion. Postoperative we found four cases of bleeding, further on in 28.3 % a superficial, in 3 % a larger and deep hematoma, but in total without any operative revision. No infection was diagnosed. In the average 17.2 (8-31) specimens were removed. After excision of 18 probes the definitive histopathologic diagnosis was clear in all cases, also, the microcalcifications were found. The underestimation rate amounted to 3 of 35 cases.Conclusions: This clinical study proves stereotactic vacuum-assisted biopsy as a relieable method for analysing indeterminate mammographically detected breast lesions, which shows lower rates of complications than conventional surgical procedures.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival. Material and Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and for MiB-1. The results were statistically analysed using Logrank-test for overall survival. Results. The mean follow-up time was 49 months. We found a significant correlation between staining results of oestrogen (p-value = 0.0005) and progesterone (p-value = 0.0003) receptor status with overall survival as well as for MiB-1 (p-value = 0.05). The correlation of staining results between biopsy specimen results and tumor material from hysterectomy was 84- 85 %. Conclusion: These well known prognostic factors are measurable on biopsy specimen material in same quality and high valence as on hysterectomy material.

Objective: We evaluated whether recurrence of intrauterine growth restriction (IUGR) in subsequent pregnancies can be predicted by histologic findings in the placenta. Methods: A total of 15,863 singleton deliveries were reviewed. A total of 32 cases of recurrent IUGR were identified. We reviewed the clinical data and the results of histomorphologic examination of the placentas in 61 mothers with 1 pregnancy complicated by IUGR, the 32 mothers with recurrent pregnancies complicated by IUGR, and 130 mothers with uncomplicated pregnancies. Maternal age > 35 years, coincidental social factors, and structural changes of the placental villi were analyzed as possible predictive factors. Results: Maternal age > 35 years, smoking, maternal diabetes or hypertension, and hypovascularization of the placenta (13% in the mothers with one pregnancy with IUGR, 28% in the mothers with recurrent IUGR and none in the control group) were risk factors for the recurrence of IUGR. Conclusion: Hypovascularization of the placental villi is an independent risk factor for recurrent IUGR in a subsequent pregnancy.

It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro. The growth kinetics of cervical cancer cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro under normoxic and hypoxic conditions. Growth factor concentrations in the cell culture medium were measured by ELISA and the secretion rates per cell were calculated. Under normoxic conditions, both the cervical cancer cells as well as the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of both angiogenic factors was significantly higher in the stroma cells than in the tumor cells (P0.05). VEGF and angiogenin secretion is significantly higher in the stroma cells under hypoxia than in the tumor cells investigated (P0.05). The presented data support the concept that in cervical cancer non-neoplastic fibroblasts could play a pivotal role in the complex process of tumor angiogenesis.

Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - Material and methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a Χ 2 -test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - Results: The mean follow-up period was 49 months. The mean age was 65 years. 21.8% of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - Conclusion: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Objective: Nitroglycerin was used successfully in the second-line treatment of severe hypertension in two pregnant patients. Case report: One patient with preexisting hypertension developed severe hypertension at 27 weeks' gestation. Treatment with dihydralazine and methyldopa caused toxic liver damage. Another patient had severe hypertension unresponsive to dihydralazine an also had uterine contractions. Both patients received intravenous nitroglycerin at a rate of 0.5-4.0 mg/h over a period of 3 days. Maternal mean blood pressure returned to an almost normal level and uterine contractions ceased. There were no negative effects on mother or fetus. Conclusion: Nitroglycerin may be considered for short-term second-line treatment of severe hypertension in pregnancy.

The value of transvaginal ultrasound in gynaecological examinations is beyond dispute. But it is of particular forensic importance that the validity of this type of imaging with regard to the reliable detection of early-stage malignancy is properly understood. Vaginal ultrasound screening in asymptomatic patients for the early detection of endometrial carcinoma is not useful from a medical point of view, nor is it cost-efficient. However, even though the validity of transvaginal ultrasound for screening has currently not been proven, the method should still be an integral part of gynaecological examinations.Die Wertigkeit der transvaginalen Ultraschalluntersuchung im Rahmen der gynäkologischen Untersuchung ist unbestritten. Es ist aber von besonderer auch forensischer Bedeutung, dass die Aussagekraft dieses Untersuchungsverfahrens im Hinblick auf das sichere Erkennen einer Krebserkrankung im Frühstadium sinnvoll eingeordnet wird. Unter Kosten-Nutzen-Gesichtspunkten ist ein generelles Screening bei asymptomatischen Patientinnen nicht sinnvoll. Zwar kann die transvaginale Sonografie das Ziel als Screeninginstrument zum gegenwärtigen Zeitpunkt nicht erreichen kann, sie bleibt aber integraler Bestandteil der gynäkologischen Untersuchung.

Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40–3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46–0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95% CI, 0.62–0.98) and a second validation cohort enriched for younger patients (n = 302; HR, 0.83; 95% CI, 0.7–0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the humoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast. [Cancer Res 2008;68(13):5405–13]

Background HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3′-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer. Methods Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors. Results A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034). Conclusion HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.

Objective The aim of this phase II multicenter study was to evaluate the safety, toxicity and efficacy of docetaxel administered weekly as first line chemotherapy in patients with recurrent or metastatic endometrial cancer. Patients and methods Thirty five patients with recurrent or metastatic endometrial cancer without previous chemotherapy were enrolled to receive three 6-week cycles of docetaxel 35 mg/m 2 /week with 2-week breaks between the cycles. Therapy response was evaluated after every 6-week cycle, and therapy was continued in case of at least stable disease. Final therapy response was evaluated after three 6-week cycles of docetaxel. Results Thirty five patients with a median age of 65 years (range, 37–80 years) were evaluable for toxicity assessment, one patient presented with severe anaphylactic reaction during the second application of docetaxel and therapy was discontinued. Subsequently, this patient received doxorubicin–cisplatin combination chemotherapy. Another patient was initially documented with uterine papillary serous cancer but secondarily confirmed as uterine carcinosarcoma. Thus, 33 patients were assessable for response. Overall response rate was 21% (3 PR and 4 CR). Three patients showed stable disease. Median TTP and OAS were 12 weeks and 43 weeks, respectively. Therapy with weekly docetaxel was well tolerated; in particular, no grade 3 or 4 hematological toxicities occurred. Conclusion Docetaxel weekly has a favorable toxicity profile, is well tolerated and shows encouraging activity in patients with advanced endometrial cancer.

Objective The success of various surgical interventions in 201 cases with recurrent vulvar carcinoma was examined in the light of patients' pretreatment, surgical therapy, plastic reconstruction, and postoperative disease course. Study design A databank of standardized clinical data was analyzed using statistical procedures. Results Therapy was selected on an individual basis according to tumor status. Recurrence at a site distant from the primary tumor, particularly in the inguinal region, indicated a markedly unfavorable prognosis. In contrast, tumors recurring locally did not exhibit any significant differences. Plastic surgery reconstruction led to improvements with respect to operability, wound healing, and survival. Conclusion Individualized reconstructive surgery of the vulva leads to good results in patients with recurrent vulvar cancer. To an even greater extent than is the case for primary therapy, plastic surgery enlarges the spectrum of feasible surgical alternatives so that a more favorable oncological outcome and excellent cosmetic results may be expected.

Objective. This study describes the surgical treatment and follow-up of 213 patients with primary vulvar cancer; particular attention is given to reconstructive surgical procedures. Methods. The clinical and pathological parameters of the patients were recorded according to standardized procedures, and the data concerning type of operation, surgical reconstruction and postoperative course of disease (recurrence-free and overall survival) were analyzed. Results. In about one-third of the cases, plastic surgery reconstruction involving skin-flaps was performed. In the present group of patients, plastic surgery procedures led to an elevated degree of operability as well as to more satisfactory results in terms of wound healing. For minor cosmetic defects, local (fasciocutaneous) skin-flaps resulted in excellent wound healing and short periods of in-patient treatment, even in patients with larger tumors. In cases exhibiting more severe wounds extending over larger areas of the vulva and its surrounding regions, similarly encouraging results were achieved using regional (myocutaneous) skin-flaps. Conclusion. The present study shows that reconstructive surgery of the vulva leads to good results in patients with vulvar cancer. Plastic surgery enlarges the spectrum of available operative therapy in vulvar cancer, especially in large tumors, and its application leads to a favorable oncological outcome as well as excellent cosmetic results in patients with vulvar cancer.

Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate.Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel.Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel.The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

Background. Carcinoma of the vagina is a rare disease, and it is even more rare in the neovagina. Nevertheless, it has been well described. The aim of this report was to analyze the reported cases and to add observations concerning a risk profile for this rare occurrence of carcinoma. Case report. The 29-year-old patient's history included congenital absence of vagina as a result of Rokitansky–Kuster syndrome. In 1987, when the patient was 17 years old, a neovagina was constructed by dissection between the bladder and the rectum, according to the Warthon method, and the apex of the neovagina was covered with Dura-mater. In 1990 the patient underwent radiation treatment with brachytherapy three times in combination with surgical treatment, because of granulation tissue in the neovagina. In 1999 several specimens of the granulation tissue were removed and histological examination showed intermediate differentiated squamous cell carcinoma. Total exenteration with pelvic and lower paraaortic lymph node dissection was performed, and the patient received a continent neobladder (Mainz Pouch I), colostoma, and sigma neovagina. Two months later in January 2000 the patient showed local recurrence and after local excision the patient received radiotherapy. The follow-up to June 2001 showed no evidence of disease. Conclusion. All patients with vaginoplasty should undergo regular 1-year follow-ups, including smear analysis because of the possibility of the development of carcinoma. Granulation tissue arising in a neovagina should be biopsied and no prosthesis should be used until lesions have healed completely. Patients who have undergone radiation of the neovagina carry an additional risk.

e15533 Background: The AGO established and updated guidelines on the assessment and treatment of endometrial cancer (EC) in 2006 and 2009. This prospective study tries to elucidate how patients wit...

10585 Background: Recently, we have identified for the first time a new putative phosphodiesterase named edi-3 that correlates with tumorigenesis in endometrial cancer. In the present study we analyzed the prognostic relevance of edi-3 in ovarian cancer. Methods: Edi-3 mRNA expression was measured by quantitative RT-PCR (TaqMan) in 62 patients with primary ovarian cancer. All patients signed informed consent, approved by the Clinical Review Board and Ethics Committee of the Medical University Berlin, Charité, Germany. The tumor specimens were collected according to the Tumor Bank Ovarian Cancer standard operating procedures. A validated systematic intraoperative documentation tool was used for the detailed documentation of all surgical procedures. Using the multivariate proportional hazard model we analyzed whether edi-3 predicts survival independent from FIGO-stage, grading, postoperative residual disease and histological type. Results: Edi-3 expression is associated with survival in the univariate Cox model (hazards ratio [HR]: 1.488, 95% confidence interval [CI]: 1.131 - 1.959, P=0.005). Interestingly, edi-3 was also predictive in the multivariate proportional hazard model adjusted for the conventional clinical factors (HR: 1.521, CI: 1.107 - 2.090, P=0.010). Conclusions: Edi-3 is a new independent prognostic factor in primary ovarian cancer with HR=1.5 (P=0.010). Its function, a possible role in inositol phosphate metabolism, will be further explored in a multi-instutional setting. No significant financial relationships to disclose.

5083 Background: Patients with recurrent or metastatic endometrial cancer have a poor prognosis. It has been shown that taxanes are active in this situation. The Aim of this study was to evaluate t...

Closed tube thoracostomy is a common and very useful procedure in therapy of acute thoracic injury. However, it is not without risk. With aggressive use of this procedure in the emergency department, the incidence of technical complications was 1 percent. Our review suggests that complications can be further diminished by the routine use of large thoracostomy tubes that are placed well up on the chest after confirmation of an open pleural space, by avoiding the use of a trocar for tube placement, and by the use of a high volume, low pressure suction system. Empyema was the most common complication associated with tube thoracostomy after trauma. It occurred in 2.4 percent of the patients. Its exact causes is not known, and the role of prophylactic antibiotics needs to be established.