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Purpose:  The aim of the present study was to determine the accuracy of breast cancer measurement with 2 D shear wave elastography (2 D SWE), B-mode ultrasound, and mammography by comparing these methods with the actual histopathological tumor size., Materials and Methods:  135 patients with proven malignant breast lesions at two centers were included in a prospective study. The maximum lesion diameter was measured by 2 D SWE, B-mode ultrasound, and mammography. After surgery, the histopathological tumor size was measured by a pathologist., Results:  The mean difference in tumor size on 2 D SWE, B-mode ultrasound, and mammography on the one hand, and the actual tumor size on the other, was -0.03 cm, 0.16 cm and 0.10 cm, respectively. Lesion size on histopathological investigation was overestimated by 2 D SWE (p = 0.004) and underestimated by B-mode imaging (p < 0.001). All three imaging methods underestimated the size of invasive lobular cancers and lesions > 15 mm; 2 D SWE was most accurate in this regard., Conclusion:  2 D SWE predicted lesion size more precisely than B-mode ultrasound or mammography. In cases of invasive lobular carcinoma, all three imaging methods underestimated lesion size, with 2 D SWE coming closest to the actual tumor size., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Objective: Synthetic meshes and acellular dermal matrices are increasingly used in implant-based breast reconstruction. The objective of this study was to determine the incidence and severity of complications following the implantation of the partially absorbable bi-component soft mesh SERAGYN® BR and assess risk factors for adverse operative outcomes., Methods: A retrospective clinical study was performed: The SERAGYN® BR soft mesh was utilized in 148 operations (skin-sparing mastectomy, nipple-sparing mastectomy, breast-conserving surgery, and secondary reconstruction after mastectomy) in four different institutions in Germany from June 2012 to February 2014. We analyzed whether the results were affected by tumor morphology (e.g., grading), patient characteristics and comorbidities, previous surgery or therapies, and use of alloplastic materials., Results: The SERAGYN® BR soft mesh was successfully implanted in 131 of 148 operations. The rate of reconstructive failure was 11.5%. The most common complication was seroma (25.7%), followed by hematoma and skin infection (each 14.2%). Wound-healing issues were detected in 13.5% cases, secondary wound infections in 10.8%. 83.8% of operations had no severe complications. Independent predictors for reconstructive failure were wound-healing issues, nipple- or skin necrosis, wound- or skin infections, a high volume of excised tissue, hematomas, seromas, and sentinel lymph node excisions. A higher body mass index was correlated with a higher rate of infection., Conclusion: SERAGYN® BR mesh can be used successfully in breast reconstructive surgery. Rates of major complications or reconstructive failure are comparable to the use of other synthetic or biological meshes.

Background/aim: Using drains after breast surgery is a preventive, but invasive measure to reduce seroma formation. A polyurethane-based tissue adhesive (TissuGlu®) might facilitate drainage-free wound healing after mastectomy in a non-invasive manner., Patients and Methods: Retrospectively, data from 84 patients (42 receiving TissuGlu®, 42 receiving a drainage) who underwent mastectomy, were collected (90 days postoperative follow-up). Study endpoints were defined as the number of fluid-related postoperative clinical interventions, cumulative volume of postoperative wound fluid, duration of hospitalization and postoperative complications., Results: In the entirety of postoperative interventions, no significant difference could be demonstrated (p=0.298). The drainage arm showed significantly less seroma aspirations (p=0.024) and complications (p=0.012). A significantly reduced length of hospitalization (p<0.001) and less cumulative wound secretion volume (p<0.001) appeared in the TissuGlu® group., Conclusion: The polyurethane-based tissue adhesive is a less invasive alternative to drain use in mastectomy., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The objective of this study was to evaluate the safety and efficacy of SprayShield™ Adhesion Barrier in preventing and/or reducing postoperative adhesion during gynecological surgery., Design: This was a prospective, controlled, blinded, and randomized study. Patient blinding was performed intraoperatively. Subjects were randomly assigned to the SprayShield™ or the control group in a 2:1 ratio., Setting: The study was conducted at the Clinic of Gynaecology and Obstetrics, at the University Hospital for Gynecology in Germany., Patients: Fifteen patients participated in this study; nine patients were assigned to the SprayShield™ and six patients to the control group., Interventions: During first operation (FLL) in the SprayShield™ group, the agent was applied to all myomectomy suture lines. Patients in the control group did not receive any anti-adhesion treatment, only good surgical practice. A second-look laparoscopy (SLL) was performed 8-12 weeks after myomectomy to evaluate adhesion formation., Main Outcome Measures: Main outcome measures were incidence, severity, and extent of uterine adhesions., Results: No significant differences were found between the two study groups., Conclusions: SprayShield™ is easy to use. No serious adverse event related to SprayShield™ was observed. Efficacy data are inconclusive regarding the performance of SprayShield™. Further studies are needed to better understand this performance.

Purpose: The aim of this study was to evaluate the quality standard of the nationwide breast ultrasound training program of the German Society of Ultrasound in Medicine (DEGUM) through objective parameters., Materials and Methods: 10 quality criteria, based on the recommendations of The National Association of Statutory Health Insurance Physicians (KBV), were defined for this study. All training units of the DEGUM received a questionnaire. The questionnaires and training material were analyzed., Results: All units met the required criteria pertaining to the trainer's qualification, duration per training course and the maximum number of participants per ultrasound machine. Only 1 course did not fulfill the required 50 % practical training time. The requirements to participate in the graduate course (200 self-made and documented cases) were not clearly conceived and a defined training log could be improved., Conclusion: DEGUM breast ultrasound training offers trainees a high level of education based on the requirements of the KBV. Despite the high quality of training, the content of course announcements could be improved and an official and structured educational index could be meaningful., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: 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., (© 2014 S. Karger GmbH, Freiburg.)

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To study T1 baseline signal intensity (SI) and contrast material enhancement kinetics of normal breast parenchyma by using dynamic contrast-enhanced (DCE) magnetic resonance (MR) mammography and to determine the influence of anthropometric measures and menopausal status on the variability of these features., Materials and Methods: Institutional review board approval and written informed consent were obtained. Between June 2008 and September 2011, 345 women (age range, 26-81 years; mean age, 51.3 years ± 11.6 [standard deviation]) underwent DCE MR mammography, with T1-weighted three-dimensional MR images (repetition time msec/echo time msec, 8.86/4.51; flip angle, 25°) acquired with a 1.5-T whole-body MR unit before and 1, 2, 3, 4, and 5 minutes after a gadobutrol bolus injection of 0.1 mmol per kilogram of body weight. Regions of interest were traced manually, and T1 SI of parenchyma was recorded. The influence of different predictors of T1 baseline SI and contrast enhancement was studied by using random-effects models., Results: T1 baseline SI varied considerably between women, with a mean of 167.7 ± 49.2 (71.4-424.7 [range]) and 175.9 ± 48.9 (51.8-458.3) in the right and the left breast, respectively (P < .01). T1 baseline SI increased linearly with age (P < .0001) and body weight (P < .0001). After contrast material delivery, relative percentage of enhancement was 8.1%, 13.8%, 18.2%, 22.1%, and 24.6% at 1, 2, 3, 4, and 5 minutes, respectively, but varied considerably between women. Contrast enhancement was 9.3% in the lowest quintile and 47.4% in the highest. Contrast enhancement increased with body weight (P < .01) but decreased in postmenopausal women (P < .01). Women with higher baseline T1 SI tended to have a higher contrast enhancement slope., Conclusion: Anthropometric measures and menopausal status contribute to a large variability in contrast enhancement of normal breast parenchyma. This might influence the interpretation of contrast enhancement kinetics of breast lesions and current strategies for determining contrast medium dose for breast MR imaging., (RSNA, 2012)

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., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: This retrospective study aimed to assess the diagnostic value of mammography, breast ultrasonography, and palpation in diagnosing fibroadenomas, making consistent use of the BI-RADS classification. The impact of breast density, patient age, and the size and palpability of the mass will be evaluated., Patients and Methods: Between January 2000 and December 2009, a total of 339 fibroadenomas suitable for inclusion in this study were diagnosed and histologically verified at our institution. Based on their BI-RADS or BI-RADS analog classification, all lesions were categorized as benign or malignant. These results were compared to the corresponding histopathological findings. Specificities were calculated for each of the abovementioned parameters. Chi-square test results with p-values < 0.05 were considered significant. Congruence between mammography and ultrasonography was assessed based on Cohen's kappa., Results: Palpation had a specificity of 100 %, mammography 83.9 %, and ultrasonography 88.2 %. Considering the parameters under investigation, ultrasonography is superior to mammography. The specificity of the ultrasonographic assessment "benign" vs. "malignant" varied with patient age and palpability of the lesion (p = 0.001 and p = 0.025). Mammography and ultrasonography were most congruent for lesions rated ACR 1 - 2 and for lesions > 1.9 cm (κ = 0.464, κ = 0.444)., Conclusion: For diagnosing fibroadenomas, ultrasonography is more specific than mammography when all examined variables are taken into account. Ultrasonography should therefore be favored, especially in younger patients. One needs to be aware of the effects of palpability and patient age on the ultrasonographic differentiation "malignant" vs. "benign". In some cases, mammography should be considered as an adjunct., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses., Materials and Methods: From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined., Results: Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P<.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P<.001 for both), without significant improvement in sensitivity or AUC., Conclusion: Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity., (© RSNA, 2012)

Background: The objective was the investigation of a possible predictive quantitative impact of initial tumor sphericity, measured by 3D sonography, on response to pre-operative chemotherapy., Patients and Methods: This 3D ultrasound study was conducted on 41 consecutive primary breast cancer patients who received pre-operative epirubicin and paclitaxel chemotherapy; the tumors were measured by 3D sonography and by pathology after chemotherapy. Sphericity was defined as the ratio of the smallest to the largest extent by 3D sonography., Results: A predictive impact of initial tumor sphericity on response to pre-operative chemotherapy was quantitatively identified for the first time. Sphericity was a significant predictor of pathological complete remission with a rank difference of 0.34 or about 1/3 i.e., spherical tumors were more likely to show successful remission., Conclusion: Tumor sphericity as defined from 3D sonography could be predictive of response to pre-operative chemotherapy regimens; prospective investigation is suggested.

Purpose: Rational therapy planning should aim to minimize the rate of axillary lymph node dissection (ALND) in patients without metastatic disease. By the same token, the frequency of sentinel lymph node biopsies (SLNB) should not be unnecessarily high in patients with axillary node disease. Preoperative axillary ultrasonography is a generally available noninvasive technique for assessing nodal status., Materials and Methods: Based on retrospective data, we analyzed the sensitivity, specificity, positive and negative predictive value, and efficiency of preoperative ultrasonography US. A total of 429 axillary ultrasonographic examinations were included, and the management decisions were based on the ultrasonographic findings. Patients with suspicious US results were scheduled for ALND, while patients with unremarkable findings underwent SLNB., Results: Axillary metastases were found in 146 of 429 (34 %) cases. In 75 of 429 (17 %) axillary examinations, ultrasonography revealed suspicious findings. In these cases, we proceeded with ALND, thereby reducing the number of SLNB by 17 %. 219 of 429 cases were classified correctly as not having metastasis, thus lowering the rate of ALND, which is associated with higher postoperative morbidity, by 51 %. Preoperative ultrasonography had a sensitivity of 53.6 %, specificity of 75.5 %, and a positive predictive value of 77.3 %. The negative predictive value was 51.3 % and the efficiency was 68.5 %., Conclusion: Ultrasonography is a moderately sensitive, but quite specific, preoperative method for assessing the axillary lymph nodes., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: This prospective study evaluates whether sonoelastography can improve B-mode ultrasonographic sizing of breast tumors. Precise measuring is important for effective therapy planning for breast cancer patients., Materials and Methods: The size of 100 surgically excised breast lesions (92 patients: 77 malignant, 23 benign) was compared to preoperative measurements. Lesions were imaged with both ultrasonographic techniques in identical planes. The largest sizes measured with each modality were compared to the largest histopathological measurements. The interobserver variability was also computed from measurements made by two examiners assessing identical planes., Results: Both ultrasonographic measuring techniques underestimate lesion size. The sonoelastography measurements were within ± 5 mm of the histological size in 70.1 % of malignant lesions, and the B-mode measurements in 57.1 % of cases. Sonoelastography leads to more accurate measurements of 13.0 % of cases (statistically not significant). A total of 22 lesions were also imaged by a second examiner. Sonoelastography had 27.3 % less interobserver variability (examiners agreed in 36.4 % of sonoelastography and in 9.1 % of B-mode results)., Conclusion: In this study there is no significant advantage of sonoelastography, although a tendency is apparent. The low interobserver variability also favors sonoelastography for preoperative diagnostics, since it may be less dependent on the observer than conventional B-mode imaging. The results of this prospective study require validation in a prospective multicenter study with larger case numbers., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Mesh reconstruction, especially in combination with vacuum-assisted closure, might improve healing and reduce the surgical morbidity of extensive inguinofemoral lymphadenectomy or extensive local resection in progressive cancer of the vulva., Cases: Radical vulvectomy combined with inguinofemoral lymphadenectomy was performed in 2 patients (P1, P2). The inguinofemoral wound bed was stabilized by polypropylene mesh implantation and sealed with vacuum closure system. In 1 patient with local recurrence of vulvar cancer (P3), local excision and stabilization of the wound were performed by mesh implantation., Conclusions: Mesh implantation fulfills 2 purposes: (1) it protects exposed vessels and the wound can be vacuum sealed; and (2) it stabilizes the surgical bed, permitting the required radical excision locally and inside the vascular compartment.

Background: In order to elucidate criteria for distinguishing benign from malignant lesions, this study correlated the ductoscopy-based macroscopic description of intraductal lesions with histopathologic results., Materials and Methods: Aiming to use diagnostic criteria consistent with previous publications, we analyzed the literature and established a uniform set of diagnostic descriptors. Based on these criteria, we subsequently analyzed and catalogued video and photographic material from 68 patients with nipple discharge, who had undergone ductoscopy followed by open surgery. For all breast lesions, the factors lesion type, number of lesions, lesion color, surface characteristics, and presence of blood or atypical vessels were reported. Based on the frequency distribution and the odds ratio, we were able to evaluate the differential diagnostic value of ductoscopic criteria in comparison with the respective histopathologic results., Results: Among the ductoscopic criteria, a fissured surface, hemorrhage or atypical vessels, and a polypoid appearance were important predictors for malignant lesions. In contrast, a smooth surface, the absence of hemorrhage and atypical vessels and a level appearance of the lesions predicted benign lesions., Conclusions: For predicting the benign versus malignant character of ductoscopic lesions, the following criteria should be used: presence or absence of blood and atypical vessels, surface type, and level versus polypoid appearance.

Objective: Laparoscopic supracervical hysterectomy (LASH) was analyzed with regard to surgical indications and outcomes., Methods: This is a retrospective analysis of the first 1,000 consecutive laparoscopic supracervical hysterectomies performed by one gynecologist from September 1, 2002 to April 30, 2006. The objective of the study was to find out to what extent the indication and the outcome of surgery changed with the increase in experience of the surgeon and whether a learning curve could be established based on the results. The demographic patient data, indication for surgery, patient history with regard to previous surgery, duration of surgery, intraoperative complications, uterus weight, and length of in-patient stay were collected from the medical records., Results: The main indication in 80.4% of cases was uterus myomatosis. The median duration of surgery was 70.9+/-26.3 minutes (95% CI, 69.2 to 72.5) with an average uterus weight of 212.5+/-177.0g (95% CI, 201 to 223.6). This was reduced from 85.4+/-25.9 minutes (95% CI, 78.5 to 92.3) in 2002 to 72.4+/-30.1 minutes (95% CI, 66.7 to 78.2) in 2006, in conjunction with an increase in average uterus weight from 192.3+/-145.4g (95% CI, 153.8 to 230.9) to 228.7+/-160.3g (95% CI, 198.1 to 259.3). Overall, one intraoperative lesion of the bladder (0.1%) occurred, and in 4 cases the surgeon had to convert to laparotomy instead, due to the size and immobility of the uterus. Sixty-eight patients had a uterus weight of more than 500 g. In 67% of the cases, surgery was performed on patients with at least one previous laparotomy, and 51.4% of the patients required further interventions., Conclusion: An experienced surgeon can rapidly learn the technique of laparoscopic supracervical hysterectomy and can safely perform it. In patients with symptomatic uterine myomatosis, previous laparotomy and/or with a uterine weight of more than 500g, laparoscopic supracervical hysterectomy is a useful alternative to total hysterectomy. There are few complications if preservation of the cervix is not contraindicated.

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.

Background: In consideration of increasing incidence by introduction of screening mammography, the prevalence of distant metastases and necessity of staging procedures in early breast cancer should be proved., Patients and Methods: A retrospective review was undertaken of 466 patients with newly diagnosed breast cancer in the period from 2003 to 2006., Results: Distant metastases were found in 22 (4.8%) patients at the time of primary diagnosis of breast cancer. None of these patients had a tumour < or =1 cm and the percentage of metastatic disease increased with local extension (pT1 1.4%; pT2 7.9%; pT3 14.3%; pT4 23.1%; p<0.001) and nodal status (pN0 1.7%; pN1 3.8%; pN2 21.7%; pN3 17.6%; p<0.001), Conclusion: Indication for bone scan, liver ultrasound and chest x-ray should be limited to patients with tumours >2 cm, or tumours >1 cm with lymph node involvement (N1-3).

Asparagus spears collected from a total of six commercial plantings in Austria during the main harvest periods in May and June of 2003 and 2004 were examined for endophytic colonization byFusarium spp., particularlyF. proliferatum. Potentially toxigenic fungi such asF. proliferatum were isolated and identified by morphological characteristics using light microscopy. Fumonisin B1 inF. proliferatum-infected asparagus spears was detected with IAS-HPLC-FLD or HPLC-MS/MS. The identity of endophytic fungi colonizing of a total of 816 individual spears was determined. The incidence of infection byF. proliferatum and otherFusarium spp. was highly dependent on location and sampling date. The dominantFusarium species among the endophytic microflora wasF. oxysporum. Other frequently isolated species includedF. proliferatum, F. sambucinum, F. culmorum, F. avenaceum andF. equiseti. The incidence ofF. proliferatum-infected asparagus spears was less than 10% at four of the six sampling locations. At the two remaining locations, 20-47% of the spears examined were infected withF. proliferatum. Further exploration of FB1 generation in asparagus is required because the low levels of FB1 (10-50 (μg/kg) detected in harvested spears in 2003 and 2004 cannot be explained by the results of this study.

Several large, well-controlled clinical trials have now established that the aromatase inhibitors (AIs), including letrozole, anastrozole, and exemestane, are more effective than tamoxifen when used as adjuvant endocrine therapy in postmenopausal women with breast cancer. Yet, it is an open question as to how these drugs should be best integrated into the adjuvant treatment regimen. Both letrozole and anastrozole have shown efficacy over tamoxifen when used as initial adjuvant therapy (initiated just following surgery for breast cancer), while exemestane and anastrozole have been used as switching adjuvant therapy, i.e., following 2-3 years of initial adjuvant tamoxifen therapy, with proven efficacy over continued tamoxifen. Studies demonstrate that recurrence risk peaks in the early period after surgery, and that distant metastases in particular, accounting for most of the early recurrences, have worse survival rates when compared with other types of recurrences. Treatments that reduce recurrences, especially distant metastases, in this early period are therefore likely to improve overall survival (OS) and reduce mortality from breast cancer. In this review, we discuss early recurrence risk among postmenopausal women with successfully treated early breast cancer, the efficacy of the different AIs in reducing early recurrences and distant metastases when incorporated into adjuvant therapy, and the evidence for increased OS when AIs are used as initial or switch adjuvant therapy.

Background: Endoscopy of the female breast, known as ductoscopy, is increasingly gaining acceptance as a diagnostic procedure worldwide. Recent technical development of ductoscopes and micro-instruments is shifting research interest from diagnostic to interventional ductoscopy. We describe novel technical aspects and the resulting possible future perspective of ductoscopy., Methods: This study comprised the analysis and review of new technical developments from research at the Technical University Munich, Germany, and others, as well as a review of the MEDLINE and COCHRANE databases for the keyword ductoscopy., Results: Diagnostic ductoscopy is performed by many breast physicians worldwide. Interventional ductoscopy, however, depends on an additional working channel and a variety of micro-instruments of 0.4-0.8 mm for procedures inside the breast duct. They are at present not available in the U.S. but are used in Germany and several other countries. Autofluorescence ductoscopy is a new imaging technique used on an experimental base for clinical evaluation to identify intraductal lesions. Laser ductoscopy for removal of intraductal papillomas and 3-dimensional intraductal tracking systems are future projects., Conclusion: Technical innovation and further miniaturization of instruments is supporting a change from diagnostic to interventional ductoscopy. A therapeutic intraductal approach as well as autofluorescence endoscopy could potentially eliminate unnecessary biopsies and offer better identification of intraductal lesions.

Background: At the time of initial diagnosis of endometrial cancer, therapeutic decisions depend on the recognition of remote metastases. Tumor markers and hepatic enzymes are frequently used to screen for metastases. This study aimed to assess the clinical value of serum concentrations of tumor markers and liver enzymes., Patients and Methods: Laboratory test results from all patients with the initial diagnosis of endometrial cancer treated in our department between 1990 and 2000 were retrospectively reviewed. Hepatic enzyme levels and tumor markers relevant for endometrial cancer were recorded. Analysis of variance and post hoc tests were used to rule out or to confirm systematic differences. Significances were examined by the Mann-Whitney test., Results: A total of 336 women were included in the analysis. Recorded data included serum concentrations of alanine aminotranspherase (ALT) (n = 228), aspartate aminotranspherase (AST) (n = 289), gamma-glutamyltranspherase (Gamma-GT) (n = 176) and alkaline phosphatase (AP) (n = 86). The following tumor markers were analysed: carcinoembryonic antigen (CEA) (n = 182), squamous cell carcinoma antigen (SCC) (n = 40), cancer-associated serum antigen (CASA) (n = 10), CA 15-3 (n = 5), CA 19-9 (n = 21), and CA 125 (n = 28). Only CEA serum levels differed significantly between patients with endometrial cancer and hepatic and pulmonary metastases at the time of initial diagnosis and patients without metastases., Conclusion: Our data show that neither the level of the tumor markers CEA, SCC, CA 15-3, CA 125, CA 19-9, CA 72-4 and CASA nor the hepatic enzymes AST, ALT, Gamma-GT and AP in routine evaluation accurately predict the presence of remote metastases.

Purpose: Although benign, radial scar/complex sclerosing adenosis is a lesion which histopathologically resembles tubular carcinoma. On physical examination, it is difficult to distinguish radial scar from a malignant tumour. Mammography cannot differentiate radial scar from malignancy. This clinical study aims to delineate the role of preoperative ultrasonography with emphasis on the question whether ultrasonography could lower the number of false-positive readings and therefore the number of open biopsies required., Materials and Methods: In this examination, we present the clinical, mammographic, ultrasonographic, and histopathological features of 6 cases of radial scars., Results: Although most authors describe radial scars as non-palpable, 2 of 6 lesions were indeed palpable. On mammograms, radial scars have a spiculated appearance, a feature observed in all of our cases. Numerous ultrasonographic characteristics are listed in the literature, but ultrasonography is not reported to have clear-cut advantages., Conclusion: Although this study did not elucidate any unique ultrasonographic features to characterise these lesions, the analysis of all ultrasonographic results made us recognise a set of "nearly specific ultrasonographic features" of radial scars. Current B-mode imaging does not appear to lead to the desirable reduction of the rate of unnecessary open biopsies.

Aim: This prospective double-blind study was designed to assess (i) if primary breast screening by ultrasonography is capable of detecting breast cancer independent of tissue density and (ii) if the rate of unnecessary biopsies remains acceptable when diagnostics are based on ultrasonography., Patients and Methods: Bilateral breast ultrasonography was performed in 448 asymptomatic women as the initial diagnostic method. Sonograms were interpreted using a set of standardized diagnostic criteria. Subsequently, mammograms were obtained. The radiologists reading the mammograms were blinded to the sonographic results., Results: Overall, 3 non-palpable breast cancers were detected by ultrasound and mammography. All 3 ultrasonographically detected breast cancers were smaller than 1 cm (0.7, 0.7, 0.6 cm). All 3 carcinomas were correctly detected by both methods. For ultrasonography, the false positive rate was 1.1% (n=5) and for mammography 0.6% (n=3). When both methods were combined, the rate of unnecessary open biopsies was 1.6% (n=7). The ratio of benign to malignant lesions was 3.7/1., Conclusion: Without prior mammography, primary high-resolution breast ultrasonography is capable of detecting non-palpable breast carcinomas in asymptomatic women at an early stage. The rate of unnecessary open biopsies is low and the ratio of benign to malignant biopsies acceptable.

Study Objective: To describe performance of breast duct endoscopy and compare the method with conventional diagnostic techniques., Design: Canadian Task Force classification III., Setting: Interdisciplinary Breast Unit of a university hospital., Patients: Consecutive and unselected series of 15 female patients including 20 breasts with nipple discharge., Interventions: Prospective data assessment on all patients with ductoscopy for nipple discharge between April 2003 to April 2004. All preoperative (mammography, ultrasonography, nipple smear) and minimally invasive (galactography, fine needle aspiration cytologic study) diagnostics were evaluated and compared with ductoscopy., Measurements and Main Results: Mammography on 20 breasts showed BI-RADS-I (5%), BI-RADS-II (50%), and BI-RADS-III (45%). Breast ultrasound scanning showed abnormalities, classified as BI-RADS-III equivalent lesions in all cases. Nipple smear showed in 69.2% a normal cytology and in most cases revealed a papilloma later (n=8/9). Unilateral galactography was performed in 46.7% who had spontaneous nipple discharge. Two galactography results were unremarkable, and open biopsy demonstrated 1 atypical ductal hyperplasia and papilloma. On 20 breasts of 15 women, 19 ductoscopies were successfully performed (95%). In 17 cases open biopsy followed ductoscopy, and 1 ductal carcinoma in situ (DCIS), 3 atypical ductal hyperplasia (ADH), 1 ductal hyperplasia without atypias, and 12 ductal papillomas were found., Conclusion: Compared to nipple smear, the diagnostic value of ductoscopy in this study is superior but marginally inferior to galactography and highly specialized breast ultrasound scanning. Therefore ductoscopy needs to be evaluated on a larger scale, preferably in multicenter trials to further determine its potential and indications.

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 microM 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 microM 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.

Study Objective: The aim of the study was to determine perioperative morbidity and complication rate after a standardized technique of laparoscopic supracervical hysterectomy (LASH)., Design: Retrospective analysis of consecutive patients (Canadian Task Force classification II-3)., Setting: Private hospital., Patients: Seventeen hundred and six consecutive patients with symptomatic uterine myomata, dysfunctional uterine bleeding, dysmenorrhea, or chronic pelvic pain., Intervention: Laparoscopic supracervical hysterectomy using a unipolar hook for dissection of the body of the uterus followed by electric morcellation., Measurements and Main Results: The main indications for LASH were uterine myomata with dysfunctional uterine bleeding (31.1%) or without (45.4%) and therapy-resistant dysfunctional uterine bleeding (21%). The mean uterine weight was 226.4 +/- 193.9 g (95% CI 217.1-235.6), the mean duration of surgery was 91.4 +/- 33.3 minutes (95% CI 89.9-93.0), and the mean duration of hospital stay was 2.15 +/- 0.63 days (95% CI 2.12-2.18). Nine hundred two (52.9%) of the patients had a history of at least one laparotomy. In 14 patients (0.82%), a conversion to laparotomy was necessary. Of these, 11 were due to the size and immobility of the uterus, one was due to severe adhesions, and two because of intraoperative complications. In total, five (0.3%) intraoperative and 20 (1.2%) postoperative complications occurred. The mean weight of the uterus in the five patients with intraoperative complications (three bladder injuries, one ureter injury, and one severe intraoperative bleed) was 818.4 +/- 911.9 g (95% CI -313.9-1950.7). In two patients who suffered trauma to the bladder, there was a history of cesarean sections (two and three, respectively). The most common postoperative complications were bleeding from the cervix and pain caused by adhesions or postoperative infection., Conclusion: Laparoscopic supracervical hysterectomy is a minimally invasive surgical method that should be regarded as an alternative to all other methods of total hysterectomy in benign conditions of the uterus (uterine myomata, dysfunctional uterine bleeding, uterine adenomyosis) as it is associated with a low perioperative morbidity and a rapid period of convalescence. Of special significance is that LASH can be performed on nulliparous patients, patients who have not previously had vaginal delivery, and patients who have had previous abdominal surgery.

Even in elderly patients, greater consideration is now being given to tumor volume reduction in locally advanced breast cancer, with increased subsequent breast-conserving surgery. Neoadjuvant endocrine therapy offers the possibility of testing therapeutic efficacy in vivo, which is of great importance for optimal adjuvant treatment. Resulting therapy modifications can be expected to increase disease-free as well as overall survival. Recent results indicate that remission rates with primary chemotherapy are significantly lower in receptor-positive than in receptor-negative breast cancer and that efficacy parameters in receptor-positive tumors tend to favor primary endocrine therapy, highlighting the increased importance of this type of treatment. Aromatase inhibitors are superior to tamoxifen in terms of clinical response as well as breast conservation rate. Results from a small number of studies suggest that prolonged preoperative aromatase inhibitor therapy for up to 12 months can increase the rate of clinical and pathological complete remissions. In conclusion, primary endocrine therapy is a valid therapeutic option for postmenopausal patients with locally advanced hormone receptor-positive breast cancer and significant comorbidity, increased risk of complications with regard to anesthesia and surgery, desire for breast-conserving surgery and/or reduced suitability for chemotherapy, as well as in very old patients.

Background: The present investigation aimed at assessing the possibility of distinguishing between malignant and benign breast lesions by measuring the signal intensity in vessels of the suspect lesions over time after administration of the ultrasound contrast agent Levovist., Materials and Methods: Levovist was administered intravenously to 21 patients with breast cancer and 12 patients with a benign breast lesion. In the subsequent ultrasound investigation (Color Power Angiography) the resulting increase in brightness over time in the vessels of the lesions was measured using the videodensitometry method. From the calculated time-brightness curves, the time to maximum brightness (T(max)), time to 90% of maximum brightness (T(90%)), maximum brightness and other time and brightness parameters were determined. The data were analyzed by means of the Mann-Whitney-Wilcoxon test. Additionally, the sensitivity and specificity were calculated for a sequence of cut-off levels for T(90%), T(max) maximum brightness and wash-in wash-out parameters., Results: The differences between the benign and the malignant lesions for the parameters T(max) and T(90%) were statistically significant. The malignant foci showed a significantly more rapid in-flow of the contrast agent (p = 0.006) than the benign lesions. The wash-in wash-out time for Levovist was significantly shorter for the malignant lesions than for the benign lesions (p = 0.02). The time difference in attaining maximum brightness was not significant (p = 0.14). The specificity and sensitivity made a more precise differentiation between benign and malignant tumors possible., Conclusion: The use of a contrast agent in Doppler ultrasound enhances the diagnostic reliability in distinguishing between malignant and benign lesions, justifying the use of a contrast agent with a high specificity (92%) such as Levovist. However, invasive pre-operative methods such as punch biopsy are not, thereby, rendered unneccessary. It is possible that the combination of Levovist and videodensitometry will make it possible to increase the specificity of breast cancer diagnosis.

The primary administration of chemotherapy leads to a reduction in size of tumors, increasing the possibility of breast-conserving surgery in both locally advanced, inoperable and primary operable mamma carcinomas. This, however, increases the rate of local relapse and the rate of mastectomy over the course of the disease, even although the EUSOMA guidelines are not exceeded. Whether the pre-surgical administration of chemotherapy with pathological complete remission actually increases the disease-free rate and overall survival remains to be determined. Further clinical studies are required to establish the reliability of sentinel lymph-node biopsy; currently, axillary lymphadenectomy is still the standard therapy. The response of the tumor to therapy, in correlation with predictive factors and the molecular-genetic profile, could make more individualized treatment regimes possible in the future.

Background: Intraparenchymal leiomyomas of the breast are quite rare. Areolar lesions are distinguished from intraparenchymal leiomyomas, which are less frequent. Clinically, leiomyomas appear as nodules; mammographically, they show up as round lesions. Reports on sonographic criteria are rare, and the criteria are nonspecific. Based on our case of an intraparenchymal leiomyoma, we describe additional sonographic features. The clinical, mammographic and sonographic characteristics of an intraparenchymal leiomyoma of the breast were evaluated. After surgery, the diagnosis was confirmed histologically., Results: The clinical presentation of our patient with deep-seated leiomyoma of the breast included skin dimpling and a reduction in tissue mobility, differing from more commonly reported characteristics. Mammographically, the lesion was dense and only partly demarcated clearly, corresponding to other reports. On breast ultrasonography, the leiomyoma appeared as a hypodense, well demarcated, inhomogeneous lesion with posterior acoustic shadowing. A central tumour vessel was visible on Doppler imaging, and Cooper's ligaments were discontinuous. Acoustic shadowing, the hypodense character, hyperechoic border and the central tumour vessel are therefore additional ultrasonographic characteristics of an intraparenchymal leiomyoma of the breast. This type of lesion is usually described as isodense to hyperdense and homogeneous, possibly containing semicystic components. Previous reports have only described posterior acoustic enhancement, but not acoustic shadowing., Conclusion: On breast ultrasonography, an intraparenchymal leiomyoma of the breast can present with posterior acoustic shadowing, hypodense echogenicity, a hyperechoic border and a central tumour vessel. Neither imaging studies nor palpation allow distinction between benign and malignant lesions.

This article reviews the role, diagnosis and treatment of Ureaplasma infections in human reproduction.

We report on a 45-year-old patient who presented with a 7 cm palpable right breast mass which had been classified as a cyst by ultrasonography. Multiple aspiration cytologies revealed no evidence of malignancy. Repeat sonography in our institution showed a lesion at 1 o'clock, 1 cm deep, and 3-8 cm from the nipple. The lesion contained a solitary cystic component measuring 3.9 x 4.1 x 4.4 cm. A 3.1 x 2.6 x 2.5 cm solid, inhomogeneous mass with irregular margins was found at the lateral border of the cyst. This mass raised suspicion of an intracystic carcinoma. Histopathologic analysis of 5 high-speed biopsy tissue cores demonstrated an invasive large-cell ductal carcinoma (G2-3). Final histopathologic assessment subsequent to breast-preserving resection and axillary node dissection confirmed the initial diagnosis: keratinizing intracystic squamous cell carcinoma (G2-3, pT2, pN0 (0/15)). The search for a remote primary squamous cell carcinoma included a chest X-ray, cystoscopy, colposcopy and PAP smear, esophago-gastroscopy, ENT consultation (laryngoscopy), and did not reveal any extramammary cancer. The postoperative management consisted of a total of 6 cycles of chemotherapy (Cisplatinum 75 mg/m (2) BSA and Paclitaxel 175 mg/m (2) BSA every 21 days) and subsequent percutaneous radiotherapy. In accordance with published reports, the diagnostic and therapeutic management was analogous to that of adenocarcinoma of the breast. However, some authors recommend the same chemotherapy as used for squamous cell carcinomas of other organs. It remains difficult to make any statements regarding the adjuvant therapy and prognosis, since this type of tumor is so infrequent, especially as an intracystic lesion.

Breast cancer is the most frequent gynecological tumor. The HER-2/neu oncogene may play a role in the prognosis and management of patients with breast cancer. In a retrospective study on 100 patients, we correlated the expression of this oncogene with the classic clinical and pathological factors. 32 % of patients exhibited overexpression of HER-2/neu. There was no significant correlation with classic parameters. This finding could indicate that HER-2/neu expression is a new independent prognostic factor. Prospective studies correlating HER-2/neu overexpression with prognosis might provide additional data.

Benign tumours in pregnancy are often "lactating adenomas". The differentiation against malignant processes is sometimes difficult. In this case report we demonstrate the diagnostic and therapeutic procedure in an 18-year old woman with multiple nodes in the right and left breast. Pregnancy makes it difficult to examine the breast with the usual methods. Because of suspect clinical and ultrasonic findings we made a core biopsy already during pregnancy. With nodes in the breast during pregnancy, ultrasound is the diagnostic method of choice. Histology by core biopsy must be made. As long as the histology corresponds with the ultrasound findings, controls are sufficient if the findings are benign. Otherwise, diagnostic exstirpation will be necessary even though the patient is pregnant. Ultrasound and biopsy are the only significant examinations in pregnancy and lactation. Mammography is contraindicated because of radiation. Assessment by palpation and NMR is problematic during pregnancy.

We report a fetal bilateral renal agenesis in a woman suffering from insulin-dependent diabetes mellitus. Early diagnosis of this lethal congenital anomaly allows well-timed termination of pregnancy. Transvaginal sonography in combination with color flow mapping render possible an accurate diagnosis of bilateral renal agenesis. Sonographic and color flow mapping features of the above described malformation as well as invasive diagnostic possibilities and causes of renal agenesis in maternal IDDM are discussed.