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PURPOSE: The rising incidence of vulvar cancer in the last decades has led to an increasing number of plastic reconstructions for vulvar/vaginal defects. MATERIAL AND METHODS: Between 2004 and 2009, 20 women with primary or recurrent vulvar/vaginal cancer, extensive VIN/AIN, large defects after wound infections or vaginal stenosis were treated with 25 vulvar flaps. We used 9 distant flaps (6 VRAM, two M. gracilis and one M. tensor fasciae latae flap) and 15 regional flaps (8 gluteal fold, 4 fasciocutaneous and 3 Singapore flaps). The major indication to use a distant flap was closure of large defects in recurrent vulvar cancer; locoregional flaps were used to cover smaller defects or to preserve vita sexualis in young women with posterior vulvar tumors. RESULTS: The preparation and insertion of a distant VRAM flap was a reliable procedure to close large defects in the mons pubic area and large defects in the vulvar area; the gluteal fold flap was used to reconstruct the vulva laterally and dorsally; vaginal and periurethral defects were reconstructed ideally with Singapore flaps. Myocutaneous advancement flaps can be used to reconstruct the posterior fourchette to prevent vaginal stenosis. Individualized planning of the reconstructive procedure is key. Severe complications were rare in our series. CONCLUSION: We conclude that individualized plastic reconstructive procedures are a safe treatment option, when performed by experienced surgical gynecologists who are familiar with plastic reconstructive techniques, to preserve sexual function or close large vulvar defects after resection for recurrent vulvar carcinoma.

After the establishment of certified breast centers, there is a legitimate question regarding the certification of surgeons. Aim of the presented study was to compare the qualifications of German breast surgeons with the training provided by different international programs. In an internet search, the training criteria of breast surgeons were evaluated and compared for the following countries and specific medical societies: EUSOMA, German Society of Senology, AWO-gyn, Italy, Austria, Switzerland, Great Britain and the USA. Evaluation criteria included training in diagnostics, the type and number of required breast surgeries, the extent of knowledge of systemic and radiation therapy, the length of training and requirements for training centers. In addition, well-known breast surgeons from each country were interviewed. Currently, only Germany and Great Britain offer a structured training program for breast surgeons. The program established by the AWO-gyn includes a definite training content based on the requirements for physicians with the specialization “gynecology”, the sub specialization “gynecological oncology” and the requirements of the Germany Society of Senology for certified breast centers. Breast surgeons certified in accordance of the AWO-gyn curriculum must not merely be able to demonstrate their ability to perform all surgical techniques but must crucially also have an extensive knowledge of the available interdisciplinary treatment modalities for breast cancer. The German AWO-gyn curriculum for certified breast surgeons provides the best international training and ensures that breast surgeons combine their surgical training with a broad knowledge of diagnostics and breast cancer therapies.

Retroperitoneal fibrosis (M. Ormond) is a rare differential diagnosis for lymphogenous retroperitoneal metastasis of ovarian cancer. We describe a case of a histologically proven retroperitoneal fibrosis (RPF) after tumor recurrence of primary adenocarcinoma of the ovary. By additional PET examination the simultaneous RPF and tumor recurrence could be diagnosed and therapeutic decisions for a second line chemotherapy could be made on the basis of minimally invasive procedures, and an otherwise extensive surgical intervention for ureterolysis could be avoided. PET should be used for optimized therapeutic management in a case of a retroperitoneal tumor formation of unclear origin during the follow up of gynecological malignancy.

Purpose: Currently, only limited preventive interventions are available to women who carry BRCA1 or BRCA2 mutations or who are at increased risk for breast and ovarian cancer. Prophylactic mastectomy and oophorectomy are, in addition to chemoprevention, the only primary prevention up to now. In this review studies of the attitudes, decision making, coping and long term satisfaction of high risk women and of the attitudes of health care professionals are the main outcome variables. Methods: The review is based on the analysis of German and English databases with a search of both medical and psychological databases until 2005. Results: Performance of prophylactic surgery for hereditary breast and ovarian cancer varies widely internationally. 3% to 67% of women at risk or mutation carriers elect to undergo prophylactic mastectomy and between 13% to 64% choose to undergo prophylactic oophorectomy. Studies examining attitudes towards prophylactic mastectomy and oophorectomy show similarly diverse results. Different counseling strategies may account for this finding. Heightened risk perception, cancer specific anxiety and physicians' recommendations affect, in addition to the objective disease risk, the decision for prophylactic mastectomy. In addition male physicians recommend prophylactic surgeries more often than female physicians. Studies focusing on satisfaction and coping with prophylactic surgery are mostly retrospective and only few studies include women, with a longer follow up. In addition to the objective risk reduction the studies suggest that prophylactic surgery is associated with a considerable reduction in psychological distress which counterbalances the impairment in body image and endocrine symptoms. Very few women regretted the decision to undergo prophylactic surgery. Conclusion: Informed decision making and time to consider is crucial when women consider prophylactic surgery. At the same time other less invasive methods of risk reduction such as chemoprevention should be extensively discussed. © Georg Thieme Verlag KG Stuttgart.

Purpose: Advances in technology have spawned monopolar, bipolar and ultrasonic tools to facilitate dissection, ligate vessels, and resect tumor tissue. The Ligasure vessel sealing system uses bipolar electric energy to seal tissue and blood vessels up to 7 mm in diameter. Methods: We have used the Ligasure system since September 2001 at 56 operations for gynecologic malignancies. Ten randomly selected operations were analyzed. Indications for surgery were carcinoma of the cervix (3 primary, 2 recurrent), ovary (n = 2), endometrium (n = 1), or vagina (1 sarcoma, 1 carcinoma). Patients underwent anterior (n = 1), posterior (n = 1) or total (n=4) pelvic exenteration, vaginal colpectomy (n = 1), or radical hysterectomy (n = 3). Blood loss and transfusion requirements, operating time and hospital stay were compared with those in a control group of 10 women operated on conventionally during the same period. Results: Blood loss and transfusion requirements were significantly less in the patients operated on with the Ligasure system compared with those operated on conventionally (2120 ± 1376 vs. 4637 ± 3746 mL, P < 0.02, and 2.8 ± 2.4 vs. 6.6 ± 5.8 units, P < 0.03, respectively). There were no severe intraoperative or postoperative bleeding complications in either group and no differences in operating time or length of hospital stay. Conclusion: Our intial experience indicates that the Ligasure system reduces intraoperative blood loss and thus seems useful for major gynecologic procedures such as pelvic exenterations. Randomized trials would appear appropriate.

Germline mutations of different genes define various hereditary cancer susceptibility syndromes. The hereditary non-polyposis colon cancer (HNPCC) and the hereditary breast and ovarian cancer (HBOC) syndromes are the major syndromes, with endometrial (EC), breast (BC) and ovarian cancers (OC) being the most abundant female tumour types. Genetic counselling and identification of high-risk families may be essential (I) to provide the best method for genetic testing, (II) to offer the opportunity to participate at specific early cancer detection programmes, (III) to inform about additive or prophylactic medication [oral contraceptives (OCPS), hormone replacement therapy (HRT)], chemoprevention [tamoxifen (TAM), raloxifen (RLX), aromatase inhibitors], or surgery and (IV) to provide individualized psychological support. To fulfill these widespread demands, an interdisciplinary counselling approach in the setting of a cancer genetic clinic seems to be the most appropriate approach. Risk estimation of lifetime disease or mutation carrier status and the use of additive, preventive or therapeutic options may be emotionally disturbing for those receiving counselling and have to be discussed extensively. OCPS reduce the risk for ovarian and endometrial cancer. HRT alone or in combination with TAM does not alter the risk for breast cancer significantly. Chemoprevention of BC for high-risk women is not as effective as expected, but not influenced by the combination of TAM and HRT. HRT and TAM both increase, while RLX decreases, the EC risk. Indications for prophylactic operations with add-back of HRT have to be individualized, risk for other cancers estimated and psychological support during the period of decision making and follow-up care have to be offered.

Background The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline–taxane–based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. Patients and methods Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms. Results With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1–3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. Conclusions Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline–taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. Clinical trial number NCT 00567554, www.clinicaltrials.gov .

In 10–30 % of cases, locoregional recurrence is accompanied by distant metastasis; a further 25 % develop distant metastasis within the year after diagnosis of recurrence. In treatment of recurrent tumor in the thoracic wall, axillary or supraclavicular disease surgery plays a major role. Since – another long-lasting courses occur even in the metastatic situation, recurrence is not an infrequent event, and therapy then needs a multidisciplinary approach. Surgical techniques such as local, myocutaneous or omental flaps and mesh graft transplantation are used to cover large defects after tumor resection. Additional and innovative modalities are combined in the management of this complex problem: locoregional or systemic chemotherapy, topical application of chemotherapy, certain radiation regimens and in otherwise resistant tumors the experimental use of photodynamic laser therapy (PDT). The most important goal hereby is to restore or at least maintain organ function and quality of life.

In recent years the indication for a mastectomy for breast cancer has been increasingly restricted. The use of plastic reconstructive techniques enhances the rate of breast-conserving therapy even for large breast tumors with excellent cosmetic results and oncological safety. The breast-to-tumor ratio and locally complete resection with free tumor margins of 1–2 cm are the most important factors in breast-conserving surgery. Different techniques of reduction mammoplasty within the concept of oncological breast surgery not only allow large tumors in large breasts to be resected, but also relatively large tumors in normal sized or even smaller breasts to be resected. Other advantages are the reduction of breast size and therefore target volume before postoperative radiation procedures as well as in cancer prophylaxis and risk reduction by reducing ipsi- and contralateral breast tissue. Reduction mammoplasty techniques with different resection areas have to be selected for individual tumor locations. The best symmetry is achieved by bilateral mammoplasty in a one step procedure with lumpectomy and axillary dissection. Oncoplastic or reconstructive surgery in the target breast is often followed by procedures to improve symmetry by contralateral reduction. Whenever possible, mammoplasty techniques with minimal scarring should be chosen out of a variety of reduction procedures.

Extremely radical and radical surgical treatment of breast cancer was investigated with regard to indication, prognosis and local recurrence in comparison to current standard breast-conserving procedures. Plastic-reconstructive techniques and innovative therapeutical approaches such as preoperative chemotherapy can extend the indications for breast-conserving therapy without loss of oncological safety. Choosing individually various oncoplastic techniques such as glandular adaptation, local or distant flaps or mammoplasty permits breast remodeling with excellent cosmetic results. We present the variety of intraglandular techniques and local flaps that enable the breast surgeon to achieve good symmetry and breast shape with minimal surgery and scarring.

Unter dem Aspekt der Pravalenz der weiblichen Adipositas von 15–25% in den Industrienationen stellt die elektive, die onkologische, aber besonders auch die notfallmasige operative Versorgung extrem ubergewichtiger Patientinnen spezielle Anforderungen an Ausstattung, Logistik und Kompetenz von Kliniken und Arzten. Das typische Spektrum gynakologischer Operationen bei Fettleibigkeit reicht von Routineeingriffen zur Behebung von Deszensus und Harninkontinenz uber grose onkologische Beckenchirurgie bis zu plastisch-asthetischen bzw. medizinisch indizierten Reduktionsplastiken. Grundsatzlich profitieren adipose Patientinnen aufgrund der deutlich geringeren Wundheilungsproblematik von den Moglichkeiten der minimal-invasiven Chirurgie. Zur Vermeidung intra-, peri- und postoperativer Komplikationen sind sowohl die apparativen Ausstattungen (z. B. entsprechend tragfahige Operationstische) als auch adipositasbedingte diagnostische und operative Besonderheiten zu beachten; ggf. sind spezialisierte operative Zentren auszuwahlen.

Background: Histopathological grading is an important part for the characterization of breast cancer with regard to prognosis and treatment options. 30-60% of breast cancer patients have a grade 2 (G2) malignancy resulting in an intermediate prognosis and the challenge of finding individualized adequate treatment options. Moreover, the lack of objectivity of the grading system is criticized. With the genetic analysis of breast cancer, the deciphering of its genes and gene expression profiling using microarray technology is a new way of classifying breast cancer Patients, Materials, and Methods. Tumor tissue from 229 breast cancer patients collected from January 2009 - June 2010 was examined. A histological grading of the tumors was determined and gene expression profiling was performed by microarray technology (Agilent Technologies). Gene expression data were reduced and a novel molecular grade index (MGI-9) was defined as a G1 versus G3 classifier by SAM (Significance Analysis of Microarray) and PAM (Prediction Analysis of Microarray). The validity of the newly defined MGI-9 as a prognostic factor was tested by applying it to three published data sets with external follow-up information for a total of 760 patients Results: The significance analysis of gene expression profiles of 229 breast cancer patients using SAM showed more than 11,000 significantly differentially expressed genes according to the grading classes G1-2-3. The number of differentially expressed genes was reduced to 228 genes by SAM analysis using only the G1 vs. G3 cases (63 patients). PAM analysis resulted in a more reduced classifier of 44 molecular probes and we could show that a subset of 9 genes gave similar classification results and could reliably used in FFPE Material. The new MGI-9 index was tested in thee external data sets (GSE1456, GSE2034 and GSE3494) and could subdivide the histological G2 group in two molecular subgroups G2A and G2B with significant impact on survival in all test scenarios. Conclusion: The results show that MGI 9-gene molecular grade index is more informative than the conventional histopathological grading system. In order to validate MGI-9 a prospective, randomized study with long-term follow-up for local recurrence rate and distant metastases is urgently needed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-02.

BACKGROUND: Neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) is an innovative method in treating patients. Proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. In this subgroup analysis long-term clinical outcome data and predictive factors were analyzed. PATIENTS AND METHODS: During 1991-1998, a total of 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or -in case of breast conservation- a 10-Gy interstitial boost with (192)Ir after loading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The impact of age, tumor grade, nodal status, hormone and growth factor receptor status (ER, PR, EGFR), p53, ki-67, HER2/neu, and bcl-2 on pathological complete response pCR and disease-free survival were examined in uni- and multivariate terms. RESULTS: Hormone receptor status, proliferative activity, bcl-2, EGFR-status and clinical tumor size had a significant impact on predicting neoadjuvant therapy success. Age, cN, grading, p53, and HER2/neu status failed to reach a significant correlation to complete remission. All examined immunohistochemical factors with the exception of EGFR, and all clinical factors displayed an univariately significant impact on DFS (disease free survival). Particularly, while HER-2/neu had no predictive value for pCR it displayed the highest impact on DFS after complete response (n = 92), even in a multivariate setting with clinical tumor size and nodal status. Complementary, p53 was the most superior immunhistochemical factor for prognosis after neoadjuvant incomplete remission (n = 223). CONCLUSION: Her2/neu is a predictive marker for overall survival independent from the pCR. It has no predictive value for the pCR. P53 is a prognostic marker for patients with incomplete remission. Prospective studies are needed to evaluate their use for decisions to further individualize adjuvant treatment after neoadjuvant radiochemotherapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-03.

Lymph node biopsy is not only important as a prognostic factor, but also influences therapy. However, axillary lymphadenectomy is often accompanied by high morbidity. The sentinel lymph node biopsy (SLN) should reduce the morbidity, but give the same prognostic value. In 97.5% cases metastasis occurs in lymph nodes (LN) of levelI first, and only less than 3% directly in LN level II. The first draining LN can be identified either by radioactive material or colouring technique.