Lutropin alpha, recombinant human luteinizing hormone, for the stimulation of follicular development in profoundly LH-deficient hypogonadotropic hypogonadal women: a review

Hypogonadotropic hypogonadism is defined as a medical condition with low or undetectable gonadotropin secretion, associated with a complete arrest of follicular growth and very low estradiol. The main cause can be traced back to an irregular or absent hypothalamic GnRH secretion, whereas only a minority suffers from a pituitary disorder. The choice of treatment to reverse this situation is a pulsatile GnRH application or a direct ovarian stimulation using gonadotropin injections. The goal is to achieve a proper ovarian function in these cases for a short time to allow ovulation and chance of pregnancy. Since the pulsatile GnRH treatment lost its former importance, several gonadotropins are in use to stimulate follicular growth, such as urine-derived human menopausal gonadotropin, highly purified follicle stimulating hormone (FSH) or recombinant FSH, all with different success. The introduction of recombinant luteinizing hormone (LH) and FSH provided an opportunity to investigate the distinct influences of LH and FSH alone and in combination on follicular growth in monofollicular ovulation induction cycles, and additionally on oocyte maturation, fertilization competence of the oocyte and embryo quality in downregulated IVF patients. Whereas FSH was known to be indispensable for normal follicular growth, the role of LH remained questionable. Downregulated IVF patients with this short-term gonadotropin depletion displayed no advance in stimulation success with the use of recombinant LH. Patients with hypogonadotropic hypogonadism undergoing monofollicular stimulation for ovulation induction showed clearly a specific role and need for both hormones in normal follicular growth. Therefore, a combined stimulation with FSH and LH seems to be the best treatment choice. In the first half of the stimulation cycle the FSH dosage should exceed that of LH by 2:1, with an inverse ratio for the second half

Benign Breast Tumours - Diagnosis and Management

With improvements in breast imaging, mammography, ultrasound and minimally invasive interventions, the detection of early breast cancer, non-invasive cancers, lesions of uncertain malignant potential, and benign lesions has increased. However, with the improved diagnostic capabilities comes a substantial risk of false-positive benign lesions and vice versa false-negative malignant lesions. A statement is provided on the manifestation, imaging, and diagnostic verification of isolated benign breast tumours that have a frequent manifestation, in addition to general therapy management recommendations. Histological evaluation of benign breast tumours is the most reliable diagnostic method. According to the S3 guideline and information gained from analysis of the literature, preference is to be given to core biopsy for each type of tumour as the preferred diagnostic method. An indication for open biopsy is also to be established should the tumour increase in size in the follow-up interval, after recurring discrepancies in the vacuum biopsy results, or at the request of the patient. As an alternative, minimally invasive procedures such as therapeutic vacuum biopsy, cryoablation or high-intensity focused ultrasound are also becoming possible alternatives in definitive surgical management. The newer minimally invasive methods show an adequate degree of accuracy and hardly any restrictions in terms of post-interventional cosmetics so that current requirements of extensive breast imaging can be thoroughly met

Nipple Discharge: Role of Ductoscopy in Comparison with Standard Diagnostic Tests

Background: This study aims to assess the role of ductoscopy for detecting intraductal anomalies in patients with nipple discharge in comparison to conventional tests and to find an effective combination of both approaches. Materials and Methods: Prior to duct excision, ductoscopy was performed in 97 women. Histologic and all other diagnostic results were compared. Sensitivity, specificity, and efficiency were calculated for all methods. These parameters were also calculated for all possible test combinations in 12 patients who had completed all tests. Results: Breast sonography reached the highest sensitivity (64.1%) and efficiency (64%); mammography had the highest specificity (100%). The sensitivity of ductoscopy was 53.2%, its specificity 60%, and its efficiency 55.1%. Among combinations of all methods, the combination ductoscopy + galactography was the most sensitive (80%). Mammography, magnetic resonance imaging, and ductoscopy were each 100% specific. Ductoscopy was the most efficient (75%) single method. Conclusion: Ductoscopy is a valuable test for diagnosing intraductal lesions in patients with nipple discharge. It is more efficient than conventional tests in patients undergoing all tests

Ductoscopic Detection of Intraductal Lesions in Cases of Pathologic Nipple Discharge in Comparison with Standard Diagnostics: The German Multicenter Study

SummaryBackground: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. Patients and Methods: Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. Results: Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). Conclusion: Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium

Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients

BACKGROUND: In most patients with ovarian cancer, diagnosis occurs after the tumour has disseminated beyond the ovaries. In these cases, post-surgical taxane/platinum combination chemotherapy is the "gold standard". However, most of the patients experience disease relapse and eventually die due to the emergence of chemotherapy resistance. Histone deacetylase inhibitors are novel anticancer agents that hold promise to improve patient outcome. METHODS: We compared a prototypic histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), and paclitaxel for their treatment efficacy in ovarian cancer cell lines and in primary patient-derived ovarian cancer cells. The primary cancer cells were isolated from malignant ascites collected from five patients with stage III ovarian carcinomas. Cytotoxic activities were evaluated by Alamar Blue assay and by caspase-3 activation. The ability of SAHA to kill drug-resistant 2780AD cells was also assessed. RESULTS: By employing the cell lines OVCAR-3, SK-OV-3, and A2780, we established SAHA at concentrations of 1 to 20 μM to be as efficient in inducing cell death as paclitaxel at concentrations of 3 to 300 nM. Consequently, we treated the patient-derived cancer cells with these doses of the drugs. All five isolates were sensitive to SAHA, with cell killing ranging from 21% to 63% after a 72-h exposure to 20 μM SAHA, while four of them were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Likewise, treatment with SAHA led to an increase in caspase-3 activity in all five isolates, whereas treatment with paclitaxel had no effect on caspase-3 activity in three of them. 2780AD cells were responsive to SAHA but resistant to paclitaxel. CONCLUSION: These ex vivo findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer in vivo

Detection of Ductal Carcinoma In Situ by Ultrasound and Mammography: Size-dependent Inaccuracy

Background: Retrospective analysis of breast cancer imaging methods is a common tool for evaluating the effectiveness of ultrasound and mammography regarding ductal carcinoma in situ (DCIS). No large number subpopulation of pure DCIS has been reported. It is however known that mammography and ultrasound underestimate tumor dimension with increasing tumor size. We aimed to quantify this discrepancy. Materials and Methods: This retrospective analysis reviewed the ultrasound and mammography data from 173 patients with DCIS at the University of Cologne - Department of Gynecology and Obstetrics between the years 2007 and 2010. Of these 173 patients, 34 fulfilled the DCIS analysis requirements and were evaluated in this study. Results: Overall, ultrasound underestimated tumor size 79.4% of the time, while overestimating only 20.6% of the time. Mammography underestimated tumor size in 50%, overestimated in 38.2%, correctly estimating in 11.8%. Over and underestimation distributions differed drastically above and a cut-off point of <= 2 cm actual tumor size, with a significant shift toward severe underestimation by both methods above a tumor size of 2 cm. DCIS misestimation was defined as the absolute value of the difference between actual tumor size and pre-surgical measurement by an imaging method. Mean DCIS size misestimation (actual tumor size <= 2 cm) was 3 mm for ultrasound and 6.2 mm for mammography. Conclusion: We support previous findings that ultrasound and mammography lose accuracy with increasing tumor size. Nonetheless, ultrasound may be more useful in estimation of DCIS size for tumors <= 2 cm than previously expected