[Transperineal ultrasound to measure cervical length of pregnant women in general and in particular with cervical insufficiency - a comparison of transabdominal and transperineal ultrasound as alternatives to transvaginal ultrasound]. / Der transperineale Ultraschall zur Messung der Cervixlänge bei Schwangeren im Allgemeinen und im Besonderen bei Cervixinsuffizienz - Ein Vergleich des transabdominalen und transperinealen Verfahrens als Alternativen zum transvaginalen Verfahren.

PURPOSE: To investigate the feasibility of measuring cervical length by transabdominal and transperineal ultrasound as alternatives to transvaginal ultrasound. MATERIALS AND METHODS: 33 pregnant women with and 28 without cervical insufficiency at 16 to 35 weeks of gestation were examined by an experienced examiner (DEGUM II) and the cervical length was measured twice at an interval of 6 months. Comparability, reliability and comfort of the patients during the examinations were taken for statistical analysis. RESULTS: There is poor agreement between transabdominal and transvaginal ultrasound (Lin's rho = 0.578), whereas transperineal ultrasound shows high correlation (Lin's rho = 0.922) to the measurements obtained transvaginally, a preference referring to the comfort scale and good reliability (ICC = 0.949). When regarding sub-groups (pregnant women with and without cervical insufficiency), transperineal ultrasound shows better results than transabdominal ultrasound. However, small cohort sizes affect the statistical validity. CONCLUSION: Transabdominal ultrasound cannot be recommended to measure cervical length. Besides providing exact measurements, transperineal ultrasound avoids contact between the cervix and the probe, is better accepted by patients and offers a simplified examination. This method is a good alternative to transvaginal ultrasound. Due to minor inaccuracies of the method, we recommend this technique only for patients with a cervix longer than 2.5 cm. For further analysis concerning patients with cervical insufficiency, large-scale studies should be performed.

Evaluation of established and new reference lines for the standardization of transperineal ultrasound.

OBJECTIVES: To examine the performance of a new reference line for the assessment of pelvic organ descent by transperineal ultrasound. METHODS: We compared our newly proposed reference line, between two hyperechoic contours of the symphysis pubis (Line 3), with the horizontal reference line proposed by Dietz and Wilson (Line 1) and the central pubic line proposed by Schaer et al. (Line 2). Ultrasound volumes of 94 women obtained in routine clinical practice were analyzed. The perpendicular distance from the reference lines to the internal sphincter and the most dependent part of the bladder base was measured for volumes obtained at rest, on pelvic floor muscle contraction, on Valsalva maneuver and during coughing. Measurements were repeated 4 months later by the same examiner. Rates of assessment were calculated, and intrarater reliability was evaluated using Bland-Altman plots and intraclass correlation coefficients. RESULTS: Line 2 had to be excluded from reliability analysis because of an assessment rate of only 12%, whereas Lines 1 and 3 could be assessed in 100% of volumes. The intrarater repeatability of Lines 1 and 3 was shown to be very similar. CONCLUSION: In this comparison of three potential reference lines for the assessment of pelvic organ descent by transperineal ultrasound, the central pubic line was shown to be inferior owing to poor visibility in our volumes. Inter-rater reliability analysis and validation studies are required to confirm our results.

ICG mapping of postoperative lymphatic leakage in the groin: a video article and literature review.

Background: Inguinofemoral lymphoceles are a common postoperative complication after inguinofemoral lymphadenectomy (LNE) and a challenge for patients as well as physicians. We report here our preliminary experience in the surgical management of a recurrent lymphocele using indocyanine green (ICG) detection, followed by robotic-assisted closure of the lymphatic leaks. Objectives: The aim of this article is to illustrate the surgical steps of ICG-assisted detection of inguinal lymphatic leaks and their surgical treatment by means of robot-assisted suturing. Furthermore, the feasibility of the approach will be evaluated. Materials and methods: A 59-year-old woman with locally advanced squamous cell carcinoma of the vulva and previous conventional bilateral inguinofemoral LNE presented with symptomatic therapy-resistant lymphoceles in the groin. After a lengthy and frustrating course of standard therapy, she was offered the off-label option surgical treatment with ICG detection and subsequent robot-assisted ligation of the leaks, using the Da Vinci robotic system™. Main outcome measures: Perioperative data, specific aspects of the surgical approach specifics, objective and subjective outcomes of the new approach. Results: The procedure was performed as planned, with no intraoperative complications or device-related issues. The postoperative course was uneventful, and the patient developed no further lymphoceles. Conclusion: Visualisation of the leakage by ICG combined with minimally invasive robotic-assisted laparoscopy is a promising therapy option. The pictures and videos demonstrate our experience in regard of the safety, feasibility, and usefulness of this procedure. Further studies will be needed, to prove the absolute efficacy of the technique and express a general recommendation in regard of this approach for the treatment of inguinofemoral lymphoceles.

[Determination of maternal and foetal serum lipid profile and placental oxidised low density lipoprotein accumulation in preeclampsia and normotensive pregnancies]. / Untersuchungen des maternalen und fetalen Serumlipidprofils und des oxidierten 'Low Density' Lipoproteins im plazentaren Gewebe bei Präeklampsie und normotensiven Schwangerschaften.

BACKGROUND: Oxidised low density lipoproteins (oxLDL) are key players in the development of atherosclerotic cardiovascular diseases. Since there are similarities between the pathogenesis of preeclampsia and atherosclerosis we hypothesised an increased accumulation of oxLDL at the materno-foetal and foeto-foetal interface within the placental tissue of preeclamptic women compared to women with normotensive pregnancies (controls). Moreover, we analysed maternal and foetal serum lipid parameters. PATIENTS AND METHODS: oxLDL was determined by immunohistochemistry in placental paraffin sections of 14 women suffering from preeclampsia (30th-39th week of gestation) and compared to 28 preterm and term deliveries (25th-40th week of gestation). 10 high power fields were chosen randomly by the newCAST software and oxLDL expression was analysed via standardised methods by 2 independent and blinded investigators. Maternal and foetal triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol were measured. Statistical examination was carried out by the Mann-Whitney test. RESULTS: oxLDL was found in villous trophoblast and placental endothelium. No significant differences were observed in expression intensity between preeclampsia and controls. Maternal and foetal triglyceride levels were significantly increased in preeclampsia compared to controls (pre-eclampsia mothers: 293 [SD 87.4] mg/dL, controls: 214 [SD 89.4] mg/dL, p=0.0097; preeclampsia foetuses: 26 [SD 16.6] mg/dL, controls: 18 [SD 10.4] mg/dL, p=0.0463). No significant differences in other lipid concentrations were found. CONCLUSIONS: We could not confirm our initial hypothesis of an increased oxLDL accumulation in placental tissue of preeclampsia. However, preeclampsia is a condition of dyslipidaemia affecting both maternal and foetal serum with implications for development and programming of cardiovascular diseases in later life.

Induction of human ß-defensins and psoriasin in vulvovaginal human papillomavirus-associated lesions.

BACKGROUND: Infections with a low-risk type of human papillomavirus (HPV) may lead to genital warts. HPV targets the basal cell layer of epithelial cells. The first line of defense is the innate immune system, which provides nonspecific protection against a variety of pathogens. The antimicrobial peptides (AMPs) α- and ß-defensins, cathelicidins, psoriasin, and RNase7 are central mediators. METHODS: The expression of various α- and ß-defensins, cathelicidin LL-37, psoriasin, and RNase7 was studied in biopsy samples from 35 patients with genital warts and 25 healthy women using quantitative real-time polymerase chain reaction and immunohistochemical analysis. RESULTS: We found a significantly higher expression of the ß-defensins hBD-1 (P = .03), hBD-2 (P < 0.01), and hBD-3 (P < .001), and psoriasin (P = .001) in condylomata acuminata, compared with normal controls. The RNA and protein levels of RNase7 did not differ between infected and uninfected samples (P = .55). The α-defensins HNP 1-3, HD5, and HD6 and the cathelicidin LL-37 were scarcely detectable in normal and infected tissue. CONCLUSIONS: The differing expression of AMPs in HPV-infected, compared with noninfected, vulvovaginal biopsy samples suggests that these peptides are important in the local immune response. Curiously, hBD-1 shows a significant induction whereas RNase7 does not, which suggests differing regulation of AMPs over the course of bacterial and viral infections.

[Using contrast inversion to extend the diagnostic value of perineal ultrasound for urethral and paraurethral pathologies]. / Die Kontrastumkehr als Methode zur Optimierung der perinealen Ultraschalldiagnostik bei urethralen und paraurethralen Pathologien.

PURPOSE: The aim of our study was to show how using contrast inversion extends the diagnostic value of perineal ultrasound, in particular with regard to paraurethral pathologies. MATERIALS AND METHODS: To assess the practical value of contrast inversion in the daily routine, 42 women with urinary incontinence underwent perineal ultrasound examination. Pictures were converted to contrast inversion and then checked for the visibility of sonographic reference points for urogynecological measurements (urethra, meatus urethrae internus, vesical base) by two independent evaluators both in B-mode and contrast inversion. Visibility was compared using a coefficient of agreement. The results were then tested for significance. In addition, in our clinical routine we detected several paraurethral pathologies (e. g. paraurethral abscess, glandula paraurethralis, urethral diverticulum), each being presented in B-mode and contrast inversion. RESULTS: There was no significant difference between contrast inversion and B-mode with regard to the reproducibility of visibility of the three sonographic reference points. Contrast inversion was superior for depicting paraurethral pathologies and postoperative anatomical findings. CONCLUSION: With respect to routine evaluation, the two modes do not reveal any significant difference. For the sonographic evaluation of paraurethral pathologies, contrast inversion provides better contour sharpness than B-mode, suggesting a higher diagnostic value for ambiguous anatomical settings. The nature of contrast inversion nevertheless facilitates misinterpretations and requires frequent comparison with B-mode pictures. In conclusion, we propose contrast inversion as an initial screen and a refinement to established diagnostic methods, such as MRI and voiding cysturethrography, not as their substitute.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations.

It is well documented that the aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course, and may also deter physicians from prescribing an AI if they feel that patients may be at risk of permanent joint damage. Patient education about the possibility of experiencing arthralgia, and effective management of symptoms if they appear, are important in helping patients adhere to AI treatment, and consequently improving breast cancer outcomes. In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose for the first time an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifying the patient's lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. Knowing that joint symptoms can be managed in most patients may encourage patient-physician communication and treatment compliance.

Feasibility and efficacy of chemotherapy with gemcitabine mono and with paclitaxel/mitoxantron in gynaecological cancers.

In this prospective study 32 patients with advanced gynaecologic tumours were treated with different schemes of chemotherapy: 15 received a combination of paclitaxel (100 mg/m2/week)/mitoxantron (6 mg/m2/every second week). Seventeen patients were treated with gemcitabine (100 mg/m2) in two different schedules, and the time of infusion was 2,2-3,3 hours or 30 minutes, respectively. Tolerability and efficacy were observed. The most common reason for reduction of the dosage or for cycle delay in the combined scheme was neutropenia. The response rate was 82%. The median overall survival was 30 weeks since beginning of the chemotherapy and 15 weeks after the last infusion. Gemcitabine in the shorter scheme led to a higher median dose rate. Toxic skin effects and hematological adverse events led to dose reduction and cycle delay in 90% of the infusions in the longer scheme. The response rate was 76%. The overall survival was one to 69 weeks with a median survival of 22 weeks. The advantages of the shorter scheme were confirmed.

[Epithelial ovarian cancer]. / Das epitheliale Ovarialkarzinom.

Ovarian cancer (OC) is associated with the highest cancer-related mortality among gynecological cancers, since nearly 2/3 of patients are diagnosed with advanced stage disease which is caused by an unspecific clinical appearance and the lack of effective early detection methods. So far only histopathological and clinical prognostic factors have clinical relevance from which FIGO-stage and the postoperative residual disease have predominant importance. Early stage OC (FIGO Ia-II) has a good prognosis with survival rates of approximately 90%, provided that the tumor is macroscopically resected and an adequate surgical staging has been performed. Additionally early stage OC patients should receive an adjuvant platinum-based chemotherapy. In advanced stage OC (FIGO IIb-IV) the aim of primary surgery is a maximum cytoreduction. Additionally, postoperative treatment is performed with carboplatin/paclitaxel for six cycles. So far there are no data to support the introduction of non-cross-resistant agents, dose escalation or prolongation of therapy. The majority of advanced stage patients relapse despite optimal primary therapy. Treatment of recurrent disease follows palliative considerations and should serve symptom control and tumor regression and especially quality of life. The prognosis of recurrent disease differs extensively according to the length of the progression-free survival and response to primary platinum-based chemotherapy and is differentiated into platinum-refractory and platinum-sensitive disease. Platinum-refractory OC generally have an extensive chemoresistance against all available cytostatic agents. Various mono-chemotherapies do not exceed response rates of 20%. In contrast, platinum-sensitive recurrent OC have a much more favourable prognosis due to response rates of 30-50% with platinum-based combination therapies. Another operation seems to be only reasonable in case of platinum-sensitive recurrent disease and if the tumor can be macroscopically resected with no residual tumor The aftercare in OC should focus on the detection of recurrent disease and the detection and therapy of maintained treatment related toxicities as well as psycho-oncological aspects.

[Malignant tumors of the uterus]. / Maligne Tumoren des Uterus.

Malignant uterine tumors are responsible for up to 9% of all new cancer cases and for 4.5% of all cancer related deaths in women. The three important uterine cancers are endometrial cancers, uterine sarcomas and cervical cancers. Endometrial cancers are typically found in elderly women and are > 70% hormone sensitive (type I), type II is often less differentiated and not hormone sensitive. Diagnosis can be achieved by vaginal ultrasound and by histology after hysteroscopy and curettage of the uterine cavity. Therapy of choice is the stage related radical hysterectomy (incl. lymphnode dissection). Postoperatively and at progressive stages endocrine and radiation therapies can be useful. Chemotherapy is only useful in not hormone sensitive and in progressive tumors. Uterine sarcomas are a rare and heterogeneous group of tumors. Therefore no clinical guidelines are available for this entity. These often aggressive tumors are hardly responding to systemic and radiation therapy. Therefore radical tumor surgery plays the main therapeutic role. Cervical carcinomas are usually growing on an underlying chronic infection with oncogenic HPV subtypes. Important co-factors for carcinogenesis are tobacco smoking, an immunodeficiency and chronic genital infections of other causes. Cervical carcinomas and their precursor lesions are easily accessible for screening tests. Many tumors are detected in early tumor stages. Preoperatively diagnostic procedures are performed to examine local and distant tumor growth. In early stages a radical hysterectomy (incl. pelvine (+paraaortal) lymphonodectomy) and in rare cases an uterus preserving surgery should be performed. Alternatively a primary radiochemotherapy can be applied. Patients with tumors in stages > or = FIGO IIb receive a primary combined radiochemotherapy.

[Benign and borderline tumors of the ovary]. / Benigne und Borderline-Tumoren des Ovars.

Alterations of the ovaries easily cause diagnostic uncertainty about relevance and consequence. Palpable or sonographic ovarian tumors are reason for various differential diagnoses. Therefore the clarification of ovarian lesions is one of the main duties in daily gynaecological practice. Although diagnostic procedures might be supplemented by CT-Scan or MRI techniques, classical bimanual examination and vaginal ultrasound scan will determine the diagnosis in most cases comparably accurate. The suspected diagnosis concerning benign or malignant lesions, should take the palpable and sonographic feature, as well as the information from the patients medical history (e.g. family history of malignant diseases (BRCA 1/2 mutations) into account. In this regard, there are no other additional parameters established. Serum tumormarkers (CA 12.5) or sonographic examinations (including Doppler) have low sensitivity and specificity. Clinical diagnostic experience seems to be crucial. Cystic lesions mostly occur in premenopausal women and commonly relapse. They are mostly normal follicle cysts, but may also be a tumor of low malignant potential (LMP-tumor) or even an invasive cancerous lesion. 20-30% of all ovarian tumors are malignant and by the time of primary diagnosis already in a about 60-70% incurable due to intraabdominal dissemination. Benign or malignant lesions may occur in every age group. Ovarian tumors at infantile age are malignant in about 15%. Most malignant tumors occur between the age of 50 to 70. The LMP-tumors occur in average 10 years earlier. Malignant ovarian lesions represent about 15-30% of all genital malignant tumors. Hormonal contraceptives, pregnancy and breast feeding seem to be protective. The persistence of ovarian cysts and tumors will be mostly examined by laparoscopic surgery. In that respect the diagnosis of LMP-tumors might be incidentally and will then have a substantial impact on the extent of the surgery and the follow up. This compilation overviews the spectrum of benign and low malignant potential tumors of the ovary and their different tissues of origin.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Differential expression of elafin in human normal mammary epithelial cells and carcinomas is regulated at the transcriptional level.

Elafin is an elastase inhibitor with a unique structure, not related to the serpin family, which includes the neutrophil elastase inhibitor. The gene was identified in this laboratory by subtractive hybridization between RNAs from human mammary tumor-derived cells and cDNAs from normal human mammary epithelial cells. Elafin is consistently expressed in normal mammary epithelial cells, but is down-regulated in most breast tumor cell lines. Restriction fragment analysis detected no gross deletions or rearrangement of the gene in any of the tumor cell lines examined. The elafin gene was cloned, and both the cDNA and the promoter region were sequenced. A major positive upstream promoter element was identified by chloramphenicol acetyltransferase assay and deletion analysis, active in normal cell extracts but not in extracts of tumor cells. These results demonstrate that differential expression of elafin in normal mammary epithelial cells and breast tumor cells is regulated at the transcriptional level. Cell synchronization experiments demonstrated that elafin mRNA is down-regulated in S phase in normal cells. These results suggest that elafin may act as an inhibitor of cell cycle progression.

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies.

OBJECTIVE: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. METHODS: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. RESULTS: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = - 0.47, ρ = - 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. DISCUSSION: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the changes were most obvious in pregnancies complicated by IUGR and only minor changes were observed in pregnancies where patients had impaired liver function, our data suggests that placental rather than maternal hepatic function strongly determines lipid and steroid levels in pregnancy.

Impact of Histopathological Factors, Patient History and Therapeutic Variables on Recurrence-free Survival after Ductal Carcinoma in Situ: 8-Year Follow-up and Questionnaire Survey.

Introduction: Ductal carcinoma in situ (DCIS) is a premalignant lesion of the glandular component of the breast and a precursor lesion of invasive breast cancer. In recent decades the incidence of DCIS has risen continuously, mainly because of more extensive screening and more advanced diagnostic procedures. There is an increasing need for evidence-based treatment guidelines which will protect patients as far as possible from recurrence or invasive cancer but also from overtreatment. This retrospective single-center clinical trial analyzed recurrence-free survival times, rates of invasive and non-invasive events, and the impact of patient history, histopathological variables and therapeutic factors on recurrence-free survival times. Material and Methods: A total of 200 patients who underwent surgery between 2000 and 2007 for pure DCIS were included in the study. As part of follow-up a questionnaire was sent to patients and their respective gynecologists. Results: In the follow-up period, 12.5 % (n = 25) of the 200 patients had recurrence (invasive or non-invasive event). Menopausal status, tumor grade and tumor size were significantly associated with recurrence. Low-grade DCIS was significantly more often hormone receptor-positive than high-grade DCIS. Patients who had postoperative radiotherapy significantly more often also received endocrine drug treatment. There was a significant association between younger patient age and drug treatment. The study found that in the investigated cohort, premenopausal women had a significantly shorter recurrence-free time compared to postmenopausal women. Conclusion: This paper summarizes the current literature on DCIS. There is a need for more prospective clinical trials to improve the prognosis of premenopausal women with large and hormone receptor-positive DCIS.

Expression of the tumor suppressor gene Maspin in human pancreatic cancers.

The tumor suppressor gene maspin, a unique member of the serpin superfamily, inhibits cell motility, invasion, and metastasis in breast and prostate cancers. Maspin is expressed in normal human mammary and prostate epithelial cells but down-regulated during cancer progression. In this study, we analyzed the expression of maspin in various human cancer cells by means of Northern blot and immunohistochemistry. Maspin gene expression proved to be up-regulated in pancreatic cancer. Maspin expression was not detected in any of 6 gastric cancers, 4 melanomas, or 6 of 7 breast cancer cell lines examined. In contrast, 5 of 9 pancreatic cancer cell lines showed maspin expression, although maspin expression was not detected in normal pancreatic tissue. Furthermore, maspin was expressed in 23 of 24 tumor specimens obtained from pancreatic cancer patients as well as all high-grade precancerous lesions (PanIN3 and intraductal carcinoma extension). In contrast, no expression was observed in normal and low-grade precancerous lesions. Our results show that maspin is a new factor associated with pancreatic cancer. In addition, the detection of maspin in pancreatic tumor tissues and its lack of expression in all normal pancreatic tissues suggests that maspin may be a useful marker of primary human pancreatic cancer.

[Aromatase inhibitors in the adjuvant therapy of breast cancer]. / Aromataseinhibitoren in der adjuvanten Therapie des Mammakarzinoms.

Breast cancer is a hormone-sensitive cancer and in most post-menopausal women hormone receptor positive. The hormone receptor status is a highly valid predictive marker of responsiveness to endocrine therapy. The standard adjuvant therapy in patients with hormone-receptor-positive breast cancer is the selective estrogen receptor modulator tamoxifen. Third-generation aromatase inhibitors are accepted as a treatment option for metastatic breast cancer. However, results from recent studies show also a benefit of this type of drugs for disease-free survival with fewer adverse reactions in the adjuvant therapy. Therefore a new therapeutic field opens for the use of 3rd-generation aromatase inhibitors. This will lead to an expansion of the indication, but the question of modality -- up-front, switch or extended therapy -- remains to be resolved.

Off-label use of misoprostol for labor induction in Germany: a national survey.

OBJECTIVE: Misoprostol is safe and effective for labor induction in viable pregnancies. Little is known about the prevalence of off-label use of misoprostol, and the reasons for using or not using misoprostol for labor induction. As such, a national survey was conducted in Germany to assess reliable data about the use of misoprostol in clinical practice. STUDY DESIGN: A prospective study was performed in 2013 using a standardized survey questionnaire. All registered departments of obstetrics and gynecology in Germany were targeted. RESULTS: Out of 783 questionnaires, 542 (69%) were returned. Three hundred and fifty-five (66%) respondents reported that they use misoprostol for labor induction in viable term pregnancies, and 183 (34%) respondents reported that they never use misoprostol for this indication. The most common reasons given for using misoprostol in labor induction were: effectiveness (40%), good patient acceptance (35%), established/well proven in clinical practice (35%) and cost-effectiveness (32%). The most common reasons given for not using misoprostol were lack of licence (off-label use, 69%) and uncertainty of the legal situation (27%). CONCLUSION: Although misoprostol is not licensed in Germany for obstetric indications, the vast majority of respondents (66%) reported that they use misoprostol for labor induction. The main reasons for not using misoprostol for labor induction in Germany are legal concerns rather than lack of scientific evidence. Cost-effective medications with evidence-based effectiveness and safety should be supported by a clear statement from national medical societies.