Gestational and Non-gestational Trophoblastic Neoplasia. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 032/049, April 2022).

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Efficacy of topical progesterone versus topical clobetasol propionate in patients with vulvar Lichen sclerosus - A double-blind randomized phase II pilot study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease that mostly affects the anogenital region of women and lowers patients' quality of life. Current standard treatment of LS is topical steroids. OBJECTIVE: To evaluate the efficacy of topical progesterone 8% ointment and compare to standard therapy with topical clobetasol propionate 0.05% in premenopausal women presenting with previously untreated early onset LS. STUDY DESIGN: Randomized, double-blind, 2-arm, single center superiority trial in premenopausal women with histologically confirmed vulvar LS who were randomized in a 1:1 ratio to receive clobetasol propionate 0.05% ointment or progesterone 8% ointment. The primary outcome was the clinical severity LS score after 12 weeks, which consists of six clinical features assessed by the physician. Secondary outcomes were the symptom severity LS score, which consists of three symptoms rated by the patient, the Short Form SF-12 physical and mental health scores, and adverse events. Response to medication was assessed by biopsy at the end of the treatment to evaluate inflammatory parameters. RESULTS: Overall, 105 women were screened, 102 underwent vulvar biopsy and 37 received a histologically confirmed diagnosis of LS and were randomized: 17 to progesterone and 20 to clobetasol propionate. At 12 weeks, the mean clinical LS scores improved from 4.6 (SD 2.0) to 4.5 (SD 1.7) in the progesterone arm, and from 4.6 (SD 2.8) to 2.9 (SD 2.2) in the clobetasol propionate arm (difference in favor of clobetasol 1.61; 95% CI 0.44 to 2.77, p = 0.009), and the mean symptom severity LS scores improved from 4.5 (SD 3.8) to 3.1 (SD 3.0) in the progesterone arm, and from 4.7 (SD 2.8) to 1.9 (SD 1.8) in the clobetasol propionate arm (difference in favor of clobetasol 1.32; 95% CI -0.25 to 2.89, p = 0.095). LS was in complete remission in 6 out of 10 patients (60%) with available biopsy in the progesterone arm, and in 13 out of 16 patients (81.3%) in the clobetasol propionate arm (odds ratio in favor of clobetasol 0.35; 95% CI 0.06 to 2.06, p = 0.234). No drug-related serious adverse event occurred during the trial. CONCLUSIONS: Topical progesterone 8% ointment is inferior to standard therapy with topical clobetasol propionate 0.05% in previously untreated premenopausal women with vulvar LS after 12 weeks treatment.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Outcome of perineoplasty and de-adhesion in patients with vulvar Lichen sclerosus and sexual disorders.

OBJECTIVE: Vulvar Lichen sclerosus (LS) is a chronic inflammatory disease in which architectural changes and symptoms like itching, soreness, pain and dyspareunia can affect quality of life and sexual activity. Perineoplasty has been shown to be effective as a supportive surgical treatment in women with refractory dyspareunia in addition to the standard topical immunosuppressive treatment. The aim of this study was to evaluate retrospectively general complaints, patient satisfaction concerning sexual activity, reduction of dyspareunia/apareunia, orgasm ability and recurrence of LS after perineoplasty. STUDY DESIGN: This study is a retrospective monocentric observational study, in which patients with vulvar LS who had undergone perineoplasty were invited to fill out a standardized questionnaire during the follow-up time. The main outcome measure is the overall patient satisfaction after surgical therapy of vulvar LS. RESULTS: Forty-one of the 70 invited patients with a median age at surgery of 58 years (18-74 years) and a median 60 years (19-76 years) at the last follow-up were evaluated. The median follow-up time was 2.3 years (1-5 years). There was a significant (p < 0.001) reduction in general complaints after surgery. Twenty-two patients were very satisfied, 15 were satisfied and 3 were not satisfied with the outcome of the surgery. Only 2 patients would not recommend the surgery. Although, there was a significant (p = 0.02) reduction in dyspareunia after surgery, 10 patients still felt pain during sexual intercourse. CONCLUSION: This is one of the largest studies reporting on long-term results of perineoplasty. It showed that perineoplasty is a safe surgical treatment option with a high satisfaction rate in patients with dyspareunia due to LS and a desire to regain sexual activity. Perineoplasty can improve sexual activity and achieve overall satisfaction in selected patients even though the recurrence rate of LS in sexually active patients remains high.

[First Diagnosis of a Squamos Cell Carcinoma of the Cervix Uteri FIGO 1B1 in Pregnancy]. / Erstdiagnose eines Plattenepithelkarzinoms der Zervix uteri FIGO 1B1 in der Schwangerschaft.

First Diagnosis of a Squamos Cell Carcinoma of the Cervix Uteri FIGO 1B1 in Pregnancy Abstract. The squamous cell cancer of the cervix uteri is one of the most frequent detected cancers in pregnancy. As the tumor is in direct contact to the pregnancy, the treatment is challenging and has to be tackled individually. So far, standard concepts or studies are missing. Treatment should be focused on the oncological security of the mother like in non-pregnant women and should be according to current guidelines. Thanks to the existing therapy options during pregnancy, it is a reasonable option to maintain the pregnancy in compliance with oncological standards. An interdisciplinary approach is therefore necessary.

Diagnosis, Therapy and Follow-up of Vaginal Cancer and Its Precursors. Guideline of the DGGG and the DKG (S2k-Level, AWMF Registry No. 032/042, October 2018).

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases.

BACKGROUND: Breast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50. METHODS: RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours. RESULTS: All four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences. CONCLUSIONS: RISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Bone in the breast? Long term toxicity 21 years after interstitial brachytherapy as a boost.

An 81-year-old patient developed an exulcerous tumor in her left breast 21 years after breast cancer treatment with lumpectomy and adjuvant radiotherapy. At the time of the initial treatment 21 years ago, whole breast irradiation was performed with a prescribed dose of 48 Gy and a maximal dose of 69 Gy. In addition, the patient received a 14.7 Gy boost with multicatheter brachytherapy as partial breast irradiation. In general, fat necrosis after radiotherapy, surgery or trauma is a minor problem for patients, but can lead to diagnostic difficulties. The incidence varies: the literature indicates that it occurs in up to 34% of cases. The direct pathogenesis is not clear; it can be due to high radiation dose to the breast, dosimetric inhomogeneities or surgical complications (seromas and inflammation). The tumor in the case described here, occurring more than two decades after the primary treatment, is a rarity in this extent and is an unusual clinical, radiological, and histological finding. It provides a good example of the need for an individualized approach to treatment.

Computer Tomography-Guided Percutaneous Indocyanine Green Injection for Intraoperative Mapping of Metastatic Suspected Lesions.

Introduction: Surgical treatment in oncology is one of the main part concerning the surveillance rate of the patient in case of tumor recurrence. Metastatic suspected lesions are mostly located in the abdomen or pelvis and are diagnosed by PET, MRI, or CT scan. Especially surgery of small lesions in recurrent disease for diagnostic or therapeutic purpose is often challenging. Material and Methods: We report a case series of 3 patients who were treated in our department due to a metastatic suspected lesion in PET-CT in follow up. For histological confirmation we performed a laparoscopy using a near infrared camera (NIR) for an improved visualization of the metastatic suspected lesion during surgical treatment. Previously the lesion was marked with an amount of Indocyanine Green (ICG) via computer tomography-guided percutaneous injection. The lesion was identified via NIR camera. While changing the camera in NIR mode, it show up as a blue spot due to the fluorescent signal. After correct identification it was removed and send to pathology. Results: In all 3 cases they confirmed the diagnosis of a metastatic lesion. Complication occur in just one case, where the metastatic lymph node infiltrated the external iliac vein, which led to a high blood loss. In this case a vascular interposition had to be done. Conclusions: Because of separate wavelengths, which are used for illumination and recording, only the marked area is visible, not the background.Due to correct identification, resection of the lesion was improved and healthy surrounding tissue could have been spared.

Intra-, peri- and postoperative complications in pelvic organ prolapse surgery in geriatric women.

OBJECTIVE: Pelvic organ prolapse is a common problem among geriatric women. Advanced age is associated with a high prevalence of comorbidities that can lead to restrictive use of surgical treatment. With rising life expectancy it is predicted that surgical treatment in these women will be seen more frequently. Inconsistently there is a lack of clinical trials giving attention to elderly women suffering from pelvic organ prolapse. The aim of this study was to quantify the rate of complications in elderly women undergoing surgery for pelvic organ prolapse. STUDY DESIGN: 72 women aged ≥75 years who underwent surgical correction for pelvic organ prolapse were included in this study. Demographics, comorbidities, intra-, peri- and postoperative severe and non-severe complications were recorded. Additionally we compared the pre- and postoperative presence of symptoms linked to pelvic organ prolapse. Follow-up for the review of pelvic floor symptoms was six month. RESULTS: The mean age was 81.4 years. Four (5.6%) of the patients had a severe intra-, peri- or postoperative complication (two bowel injuries, one bleeding requiring blood transfusion, one resuscitation). All women with severe complications showed no persistent problem at the time of discharge or during the follow-up period. There was a significant postoperative decrease in pelvic organ prolapse connected symptoms, such as stress urinary incontinence (p = .013), voiding dysfunction (p < .001), recurrent urinary tract infection (p = .001) and rectal outlet obstruction (p = .006). CONCLUSION: Elderly women undergoing an operation for pelvic organ prolapse have a low risk of complication and benefit from surgery. Age alone should not be a contraindication to surgery.

Incidence Trends of Cervical Cancer and Its Precancerous Lesions in Women of Central Switzerland from 2000 until 2014.

OBJECTIVE: Cervical cancer (CC) screening by Pap smears has led to a decrease in the incidence of CC worldwide. Indeed, the incidence of CC in Switzerland is very low; however, there is a lack of data to evaluate the efficiency of the Pap smear as a screening tool. Until now, only Pap smears have been used and other methods such as the presence of an infection with HPV have not been integrated into the routine screening. The aim of this study is to evaluate trends in the incidence of CC and its precancerous lesions in Central Switzerland, which represents a rural region, with those in urban regions and the entire country of Switzerland. METHODS: All conizations and CC registered between 2000 and 2014 at the Institute of Pathology at the Cantonal Hospital of Lucerne have been included in our study. The incidence of CC and its precancerous lesions have been categorized according to age, stage, morphology, and study period. Age-standardized incidence in the Canton of Zurich and the entire country served as reference for the assessment of trends in CC incidence in the study region. RESULTS: In Central Switzerland, the number of conizations performed annually has more than doubled over the observed 15 years. There has been a significant increase in precancerous lesions, which were found in approximately 50% of conizations. The total number of CC diagnosed by conization increased by 37.5% and the total of CIN3 increased by 130%. Age-standardized incidence of CC and CIN3 increased from 2.4 to 3.3/100,000 and from 11.6 to 26.9/100,000, respectively. The incidence of CC was lower in Central Switzerland compared to incidence in the Canton of Zurich and in Switzerland generally. CONCLUSION: Approximately 50% of all conizations were performed on women without serious precancerous lesions. For this reason, we recommend the adaptation of screening modalities and the use of risk stratification to avoid overtreatment. In light of the forthcoming implementation of an HPV vaccination program, our data provides important baseline information.

Vulvar lichen sclerosus in women is associated with lower urinary tract symptoms.

INTRODUCTION AND HYPOTHESIS: Lichen sclerosus (LS) is thought to be primarily a disease of postmenopausal women. Little is reported about lower urinary tract symptoms (LUTS) in association with LS. The aims of this study were to evaluate the odds of having LS-associated LUTS and to identify the predominant type of LS-associated bladder dysfunction. METHODS: This was a cross-sectional study with two cohorts investigating the association between LS and LUTS and the predominant type of LS-associated bladder dysfunction. RESULTS: The odds of LUTS in women with LS were more than four times higher than in women without LS (OR 4.5, 95% CI 2.6-8.0; p < 0.0001). There was no significant difference in the occurrence of LUTS between women who experienced the first LS symptoms before and after the age of 50 years (36% and 53%, respectively, p = 0.14), or in the occurrence of the different types of LUTS between women with and without LS (p = 0.3). The most common type of LUTS was overactive bladder (OAB) in both women with LS (67.3%) and without LS (60%). The most prevalent type of LS-associated LUTS was OAB. CONCLUSIONS: The odds of developing LUTS (self-reported) are four times higher in women with LS than in those without. The predominant type of LUTS in women with and without LS is OAB.

First international consensus conference on standardization of oncoplastic breast conserving surgery.

PURPOSE: To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology. METHODS: A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained. RESULTS: The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient. CONCLUSIONS: When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.

Should Groin Recurrence Still Be Considered as a Palliative Situation in Vulvar Cancer Patients?: A Brief Report.

OBJECTIVE: To assess survival after groin recurrence in patients with vulvar cancer in the transition period of the implementation of the sentinel lymph node biopsy procedure. Recurrence of groin metastases in vulvar cancer patients is assumed to be lethal. It is unknown if early detection of relapse and multimodal treatment strategies improve the outcome of patients with groin recurrence. METHODS: Multicenter retrospective cohort study of patients with recurrent vulvar cancer who presented with groin and/or pelvic lymph node metastases between 2000 and 2014 at 3 tertiary referral hospitals. Our primary outcome was to assess survival after groin recurrence of vulvar cancer and the influence of multimodal treatment. All analyses were done using Stata 12 (Stata Corporation, College Station, Tex). Hazard ratios (HRs) and their corresponding 95% confidence intervals were calculated using a Cox proportional hazards model. RESULTS: We identified 30 patients with a median time from diagnosis to groin recurrence of 10 months. The median follow-up of patients who were alive at the time of analysis was 22 months (range, 9-123 months). A Kaplan-Meier estimate showed an overall survival rate of 50% after 7 years. Patients with multimodal groin relapse treatment performed better than those with single-mode treatment (HR, 0.25; P = 0.037). Lymph node metastases at diagnosis were also associated with lower survival (HR, 6.11; P = 0.020). We observed a trend toward lower survival with a tumor size greater than T1 (HR, 2.55; P = 0.111). The time from diagnosis to groin recurrence had no influence on survival (HR, 0.99; P = 0.561). CONCLUSIONS: Close follow-up visits for at least 2 years are important to detect recurrent disease in groin and pelvic lymph nodes. Treatment of recurrent groin metastases should no longer be considered as a palliative situation--given that one half of the patients will have long-term survival after multimodal treatment strategies.

Acellular Dermal Matrix (Permacol®) for Heterologous Immediate Breast Reconstruction after Skin-Sparing Mastectomy in Patients with Breast Cancer: A Single-Institution Experience and a Review of the Literature.

OBJECTIVE: Skin-sparing mastectomy (SSM) with immediate heterologous reconstruction is a safe oncological option in surgical therapy of early breast cancer. Permacol® is an acellular dermal matrix (ADM) placed between the implant and the skin to improve lower pole projection and implant coverage. The aim of our study was to evaluate the outcome with a focus on patient satisfaction after 6 months and to analyze physical changes of ADM. METHODS: 10 patients who underwent SSM with Permacol® were analyzed retrospectively. All patients were followed using a satisfaction questionnaire and an ultrasound evaluation of the tissue thickness of the pectoralis muscle and the Permacol®. RESULTS: No intraoperative complications were observed. One patient required removal of the implant for necrosis after 3 months. Half of the patients underwent secondary corrective surgery. A statistically significant thinning of the pectoralis muscle was observed, compared to the thickening of the Permacol®. A majority of the patients were satisfied with the operation, and we found a correlation between lower body mass index and patient satisfaction. CONCLUSION: In our small case series Permacol®-assisted immediate reconstruction is shown to be an option for selected cases. Physical changes of Permacol® result in a symmetrical coverage of the implant, which may improve cosmetic outcome.

Predictive factors for preterm delivery under rural conditions in post-tsunami Banda Aceh.

OBJECTIVE: To assess the risk for preterm deliveries <37 week of gestation and associated prevalence of vaginal infection in a rural setting after the tsunami in Banda Aceh, Indonesia. METHODS: Wet mount microscopy, vaginal pH and vaginal swabs for microbiological culture were collected in pregnant women during the 2nd trimester from February to June of 2005 in four temporary outpatient clinics and the patients were followed up until delivery. RESULTS: One hundred and fifty-nine pregnant patients were screened. Sixty-two could be followed up until delivery. Thirty-nine (62.9%) delivered at term and 23 (37.1%) delivered prematurely. Significant risk factors for preterm delivery were a history of preterm delivery and group B streptococcus infection. Increased vaginal pH alone had no significant influence on preterm delivery, although there was a trend. CONCLUSION: The rate of preterm delivery was high in this cohort. We suggest risk stratification for preterm delivery in rural conditions by performing a vaginal pH and wet mount microscopy. If either is suspect we suggest collecting a vaginal swab for microbiological culture for targeted treatment. Patients with a history of preterm delivery are at increased risk and should be monitored closely.

Leupaxin is expressed in mammary carcinoma and acts as a transcriptional activator of the estrogen receptor α.

Leupaxin belongs to the group of paxillin proteins and was reported to play a major role in the invasion and migration of prostate cancer cells. In the present study we were able to show by using a cDNA cancer profiling array that leupaxin is upregulated in breast and endometrial cancer, whereas downregulation of leupaxin was observed in lung cancer. In addition, immunohistochemical studies using a leupaxin-specific antibody on human breast cancer specimens (n=127) revealed that leupaxin is expressed mainly in invasive ductal carcinomas and ductal carcinoma in situ (40 and 49% respectively), and only in a minority of lobular mammary carcinomas. To further investigate the role of leupaxin in the progression of breast cancer the expression of leupaxin was analysed in six breast cancer cell lines. The estrogen receptor α (ERα)-positive HCC70 and the ERα-negative MDA-MB­231 cells showed leupaxin expression on the RNA and protein level. Leupaxin localizes in these mammary carcinoma cells at focal adhesion sites and shuttles between membrane and nucleus via its LD4 motif as major nuclear export signal. Interaction partners of leupaxin in the nucleus represent the estrogen receptors ERα and ERß. Both ERα and ERß bind to the LIM domains of leupaxin via their AF-1/DNA binding domains. Furthermore, leupaxin is able to induce transcriptional activity of ERα independent of the presence of estradiol. The specific downregulation of leupaxin expression using siRNAs in mammary carcinoma cells resulted in reduced migratory capability and diminished invasiveness whereas no effect on proliferation was observed. Collectively, these results show that leupaxin has particular influence on the progression and invasion of breast cancer cells and may therefore represent an interesting candidate protein for diagnosis and therapeutic interventions.

Safe vaginal uterine morcellation following total laparoscopic hysterectomy.

The minimally invasive approach for hysterectomy with proven benefits and lower morbidity has become the gold standard, even in women with large uterine masses. Most women with a malignant condition present with abnormal vaginal bleeding and/or suspicious imaging such that few are diagnosed by final histopathology after surgery. However, if a malignancy is not diagnosed preoperatively, intraabdominal morcellation for uterus extraction has an increased risk for potential tumor spread and peritoneal metastases, especially in cases of unexpected leiomyosarcoma. We describe a simple method to wrap the uterus in a contained environment with a plastic bag through the posterior vaginal fornix prior to conventional coring morcellation for vaginal extraction in total laparoscopic hysterectomy. We further describe our experience with a risk stratification and treatment algorithm to implement this procedure in daily routine. A video and an illustrating sketch demonstrate the simplicity and safety of the procedure.