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Background: Deficiencies in the merging process of the paramesonephric ducts as part of the embryonal development lead to anomalies of the uterus, cervix, fallopian tubes and proximal vagina (Müllerian malformations). The co-occurrence with cervical cancer is rare and there are no standardized protocols for managing urogenital anomalies in the realm of oncologic treatment for gynecological carcinomas., Case Report: A symptom-free 41-year-old woman (gravida 0) presented at our clinic with an externally obtained AGC-FN (atypical glandular cells - favor neoplastic) finding in the Papanicolaou (Pap) smear test and persistent positivity for human papillomavirus (HPV) type 16. Sample biopsies from the portio vaginalis uteri confirmed a cervical intraepithelial neoplasia (CIN) III/ high grade squamous intraepithelial lesion (HSIL), invasive carcinoma could not be ruled out. The examinations revealed the incidental finding of a uterus didelphys and renal agenesis on the left side. After cervical conization, the patient was diagnosed with squamous cell carcinoma of the cervix. Guideline-compliant treatment with laparotomic hysterectomy according to Piver type II following a staging laparoscopy with sentinel lymphadenectomy was performed. A customized protocol was used for the indocyanine green (ICG) injection as part of the sentinel lymph node examination, tailored to the patient's anatomical characteristics., Discussion: Müllerian malformations may impede detection and treatment of gynecological carcinomas. Individualized therapy planning is necessary to meet the anatomical peculiarities of the genital anomaly. In instances of concomitant urinary tract anomalies, protective measures are imperative to safeguard normal kidney function., Conclusion: The current case demonstrates the successful implementation of guideline-compliant therapy for early-stage cervical cancer in an individual with Müllerian malformation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

In precision oncology, reliable testing of predictive molecular biomarkers is a prerequisite for optimal patient treatment. Interlaboratory comparisons are a crucial tool to verify diagnostic performance and reproducibility of one's approach. Herein is described the design and results of the first recurrent, internationally performed PIK3CA (phosphatidylinositol-4,5-bisphosphate 3 kinase catalytic subunit α) breast cancer tissue external quality assessment (EQA), organized by German Quality in Pathology GmbH and started in 2021. After the internal pretesting phase performed by the (lead) panel institutes, in both 2021 and 2022, each EQA test set comprised n = 10 tissue samples of hormone receptor-positive, human epidermal growth factor receptor 2-negative invasive breast cancer that had to be analyzed and reported by the participants. In 2021, the results were evaluated separately for German-speaking countries (part 1) and international laboratories (part 2). In 2022, the EQA was performed across the European Union. The EQA success rates were 84.6% (n = 11/13), 88.6% (n = 39/44), and 87.9% (n = 29/33) for EQA 2021 part 1, part 2, and EQA 2022, respectively. The most commonly used methods were next-generation sequencing and mutation-/allele-specific qualitative PCR-based assays. In summary, this recurrent PIK3CA EQA proved to be a suitable approach to obtain an international overview of methods used for PIK3CA mutation analysis, to evaluate them qualitatively, and identify the strengths and weaknesses of individual methods., Competing Interests: Disclosure Statement A.H. had an advisory role and received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme (MSD), Roche, Cepheid, Qiagen, Agilent, Diaceutics, Lilly, AstraZeneca, Boehringer Ingelheim, Abbvie, Jansen-Cilag, Pfizer, and Ipsen. R.E. has received honoraria from Roche, Eisai, Pfizer, BioNTech, Veracyte (PROCURE), Diaceutics, Mindpeak, AstraZeneca, MEDAC, and Novartis. The institution of A.H. and R.E. conducts research for AstraZeneca, Roche, Janssen-Cilag, NanoString Technologies, Biocartis, ZytoVision, Novartis, Cepheid, Mindpeak, MSD, Gilead, palleos healthcare, Owkin, and BioNTech. U.L. had an advisory role and received honoraria from AstraZeneca, Bristol Myers Squibb, GSK, Novartis, Servier, and ThermoFisher., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: A lot of studies use the second-to-fourth digit length ratio (2D:4D) as a biomarker for intrauterine androgen load to predict behavioral and mental health problems. Thus, knowledge of 2D:4D's metric properties, namely reliability and validity, is essential., Method: 2D:4D handscans were available from 149 adolescents (M = 13.32 years, SD = 0.35) and their mothers. For 88 adolescents, there were also primary-school age handscans (M = 7.87 years, SD = 0.68). Prenatal risks for the 1st to 3rd trimesters were recorded during the 3rd trimester of pregnancy (alcohol exposition: meconium biomarker and maternal self-report; nicotine exposition: maternal self-report; maternal depressive symptoms and subjective stress: questionnaires)., Results: The 2D:4D ratio was highly stable from childhood to early adolescence. However, both developmental and sex effects were present: The 2D:4D ratio increased with age and was higher in adolescent girls vs. boys. Significant 2D:4D mother-child associations were found for girls. Significant main effects could be found for the prenatal risk factors alcohol (self-report) and nicotine consumption., Conclusion: In line with earlier studies, the 2D:4D biomarker proved to be an inter-individually stable measure with an intra-individual increase from childhood to early adolescence. Sex differences in adolescence and associations with maternal prenatal health behaviour underline the validity of the biomarker. Findings on heritability emphasize the importance of interpreting 2D:4D results in a sex-specific manner., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Research Question: Which is the optimal extraction method for isolating and quantifying circulating cell-free DNA (ccfDNA) from patients with endometriosis? Endometriosis is a common benign disease, associated with pain, infertility and reduced quality of life. Endometriosis is also a known risk factor for various cancers. Robust biomarkers for early detection and prediction of prognosis, however, are lacking. CcfDNA is an easy to obtain biomarker associated with prognosis of cancer patients and enables non-invasive analysis of somatic mutations. Recently, elevated levels of ccfDNA were detected in patients with endometriosis., Design: Two different ccfDNA extraction methods were compared: Maxwell RSC ccfDNA plasma kit (Maxwell) and QiAamp minElute ccfDNA mini kit (QIAamp). The ccfDNA and circulating mitochondrial DNA (mtDNA) quantities from 34 patients diagnosed with endometriosis were analysed. Fluorometric measurement and quantitative reverse transcription polymerase chain reaction (qRT-PCR) of short and long ALU and mtDNA fragments were used to quantiy ccfDNA., Results: The yield of ccfDNA isolated with the Maxwell method was significantly higher compared with the QIAamp method (P < 0.0001). Integrity of ccfDNA was significantly higher in the QIAamp isolate (P < 0.0001). Recovered mtDNA was not significantly different between both extraction methods used., Conclusions: The choice of extraction method can significantly influence the ccfDNA output and integrity. Both methods, however, enabled isolation of sufficient ccfDNA for further downstream applications. With this approach, isolation of ccfDNA could enable the non-invasive detection and analysis of somatic mutation within endometriosis tissue., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients., Methods: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status., Results: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect., Conclusions: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC., Competing Interests: Declaration of competing interest Peter A. Fasching reports research grants from Novartis and BioNTech and personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, AstraZeneca, Puma, Eisai, Merck Sharp & Dohme, and Myelo Therapeutics. Carolin C. Hack reports personal fees from Roche and Novartis. Julius Emons reports personal fees from Novartis, Pfizer and Eisai. Arndt Hartmann has received honoraria from BMS, MSD, Roche, AstraZeneca, Boehringer Ingelheim, Abbvie, Jansen-Cilag, Diaceutics, Cepheid, Lilly, Agilent, and Ipsen. Ramona Erber has received honoraria from Roche, Eisai, Pfizer, and Novartis and travel grants from BioNTech. The institution of Arndt Hartmann and Ramona Erber conducts research for AstraZeneca, Roche, Janssen-Cilag, NanoString Technologies, Novartis, Cepheid, and BioNTech. All the other authors declare that they have no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor-positive, HER2-negative (HR + HER2-) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported., Methods: The PRAEGNANT registry was used to identify advanced HR + HER2- BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed., Results: CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy., Conclusions: In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET., Competing Interests: Declaration of competing interest A.S. received honoraria from Roche, AstraZeneca, Aurikamed GmbH, Celgene, ClinSol Research GmbH, Connectmedica Sp.Z o.o., Deutsche Gesellschaft für Senologie GmbH, if-kongress management gmbh, I-MED Institute GmbH, Lilly Deutschland GmbH, Medicultus GmbH, med publico GmbH, MSD Sharp & Dohme GmbH, onkowissen.de GmbH, Pfizer GmbH, Schattauer Verlag GmbH, Promedicis GmbH, Tesaro Bio Germany GmbH, W. Zuckschwerdt Verlag GmbH. J.E. received honoraria from AstraZeneca, Celgene, Novartis, Lilly, Pfizer, Pierre Fabre, Roche and TEVA and travel support from Celgene, Pfizer, TEVA, and Pierre Fabre. D.L. received honoraria from Amgen, AstraZeneca, Celgene, Lilly, Loreal, MSD, Novartis, Pfizer, Tesaro, Teva. M.W.B reports support from Novartis, Merck Sharp & Dohme, AstraZeneca, Roche, Amgen, Eisai, paid to his institution. E.B. received honoraria from Novartis, Celgene, Riemser, Pfizer, Hexal, Amgen, onkowissen.de for consulting, clinical research management or medical education activities. P.A.F. received honoraria from Novartis, Pfizer, Roche, Amgen, Celgene, Daiichi-Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma and Teva. His institution conducts research with funding from Novartis and Biontech. T.N.F. reports personal fees from Roche, personal fees from Novartis, personal fees from Pfizer, personal fees from Daichii Sankyo, personal fees from Lilly, personal fees from MSD, outside the submitted work. P.H. received honoraria, unrestricted educational grants and research funding from Amgen, AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, and Roche. A.D.H. received honoraria from Teva, GenomicHealth, Celgene, AstraZeneca, Novartis, Pfizer, and Roche. C.H. received honoraria from Amgen, Celgene, Oncovis, Roche, and Pfizer. J.H. received honoraria from Astra Zeneca, MSD, Lilly, travel grants from Novartis and research grants from Novartis, Celgene. E.R. reports personal fees from Roche, Pfizer, Amgen, Novartis, Tesaro, Astra Zeneca, Celgene, Pierre Fabre and Riemer, non-financial support from Olympus GmbH, personal fees from Riemser, outside the submitted work. W.J. received research grants and honoroaria from Novartis, Pfizer, Amgen, Chugai, Roche, Genomic-Health, AstraZeneca, Lilly. H.-C.K. received honoraria from Carl Zeiss meditec, TEVA, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, and Genomic Health. C.M.K. received honoraria from Amgen, Axios, Roche, Teva, Novartis, MSD Sharp & Dohme, Mundipharma, NewCo, Pfizer, Riemser, and ZytoService, research grants from Amgen, Axios, Novartis, MSD Sharp & Dohme, NewCo, Pfizer, and ZytoService, and travel support from Amgen, Paxman Inc., PharmaMar, and Pfizer. M.P.L. has participated on advisory boards for AstraZeneca, MSD, Novartis, Pfizer, Eisai, Genomic Health, Tesaro and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac and Eisai. V.M. received speaker honoraria from Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Novartis, Roche, Teva, Janssen-Cilag and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Tesaro and Nektar. N.N. received consultancy honoraria from Janssen-Cilag and travel support from Novartis. F.O. received speaker and consultancy honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer, Celgene, Cellex, Chugai, Gilead, Hexal, Ipsen, Janssen-Cilag, Merck, MSD, Novartis, Riemser, Roche, Tesaro, Teva. H.T. received honoraria from Novartis, Roche, Celgene, TEVA, and Pfizer and travel support. F.-A. T. received honoraria from Astra Zeneca, Genomic Health and Novartis. C.T. received honoraria from Amgen, Astra-Zeneca, Celgene, Novartis, Pfizer, and Roche. M.U. reports support paid to his institution from Abbvie, Amgen GmbH München, Astra Zeneca, BMS, Celgene GmbH München, Daiji Sankyo, Eisai GmbH München, Janssen Cilag, Johnsen&Johnsen, Lilly Deutschland, Lilly Int., MSD Merck, Mundipharma, Myriad Genetics GmbH Zürich, Odonate, Pfizer GmbH Berlin, PUMA Biotechnology, Riemser, Roche Pharma AG, Grenzach Wyhlen, Sanofi Aventis Deutschland GmbH, Sividon Diagnostics Köln, TEVA Pharmaceuticals Ind. Ltd. und. Berlin(.)P.W. received honoraria from Amgen, AstraZeneca, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, TEVA, Eisai Clovis and Tesaro. She participated in advisory boards of Amgen, AstraZeneca, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, TEVA, Eisai Clovis and Tesaro. Her institution received research grants from Amgen, AstraZeneca, MSD, Novartis, Pfizer, Pharmamar, Clovis and Tesaro. R.W. received honoraria from Agendia, Amgen, Astra Zeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Esai, Genomic Health, Glaxo Smith Kline, Lilly, MSD, Mundipharma, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Seattle Genetics, Tesaro Bio, Teva. M.W. received speaker honoraria from AstraZeneca, Celgene, and Novartis. S.Y.B. reports personal fees from Novartis and Pfizer, both outside the submitted work. All remaining authors (J.S., E.K., M.G., L.H., B.V., D.W.) have declared that they do not have any conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest S·Y.B. has received honoraria from Pfizer and Novartis. W.J. has received honoraria and research grants from Novartis. A.D.H. has received honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, and Pfizer. R.W. has received honoraria and research funds from Novartis. S.K. has received honoraria from Roche, Celgene, Amgen, and AstraZeneca and funding support from Roche. C.T. has received honoraria from Novartis, Pfizer, and AstraZeneca. M.P.L. has participated on advisory boards for AstraZeneca, MSD, Novartis, Pfizer, Genomic Health, and Roche and has received honoraria for lectures from Lilly, Roche, Novartis, Pfizer, Genomic Health, AstraZeneca, medac, and Eisai. P.G. has received honoraria from Novartis and financial support for symposia from Novartis, Roche, and PharmaMar. H.-C.K. has received honoraria from Carl Zeiss meditec, TEVA, Theraclion, Novartis, Amgen, Astra Zeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, and Genomic Health. D.S.-B. has received honoraria from Novartis. M.W.B.‘s institution has received research grants from Novartis. T.F. has received honoraria from Pfizer, Novartis, Roche, and Amgen. P.A.F. has received honoraria from Roche, Pfizer, Novartis, and Celgene. His institution conducts research for Novartis. N.N. has received honoraria from Janssen-Cilag, Novartis and Teva. All of the remaining authors have declared that they have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Is ovarian tissue cryopreservation (OTC) for fertility preservation in prepubertal and adolescent girls safe, and who would benefit most from the procedure?, Design: Survey and retrospective study including patients who had OTC under the age of 18 years in a single centre for fertility preservation. Serum anti-Müllerian hormone levels were measured as a marker for detection of diminished ovarian reserve., Results: Fifty-three from 102 women participated in the survey (12 deceased, 19 declined, 17 unreachable, 1 palliative). The average age at OTC was 14.8 ± 2.3 (range: 6-17) years and at survey 21.9 ± 4.3 (range: 16-33) years. Ovarian tissue retrieval (laparoscopy: n = 45, laparotomy: n = 8) was without complications in 52 cases. In 23 (53.5%) of the 43 women who were post-menarchal at OTC, transient amenorrhoea occurred. At survey, 15 women reported a regular menstrual cycle, 25 used oral contraceptives, 9 women reported hormone replacement therapy due to primary ovary insufficiency and 4 had amenorrhoea. Two patients reported the birth of a healthy child after IVF, while 51 patients are still childless, mostly due to their young age (mean: 21.2 years). To date, one patient has had transplantation of the ovarian tissue (17 years at cryopreservation). Forty-nine of the interviewees would again decide on OTC, while three argued against it on the basis of the previous financial cost; one woman was unsure., Conclusions: Children with cancer may be at risk for gonadal insufficiency. OTC is practically the only technique that can be offered to young girls. The procedure is safe and well accepted., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood., Material and Methods: Here we re-evaluated the impact of tumor size, nodal stage and tumor subtype on disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) in a retrospective analysis using data from the adjuvant SUCCESS A trial. Subgroup analyses were conducted to assess whether the effect of tumor size and nodal stage on survival depended on tumor subtype., Results: Increasing tumor size, higher nodal stage and triple negative breast cancer (TNBC) were associated with unfavorable prognosis (all p < 0.001). There was no significant interaction between tumor subtype and tumor size (p > 0.5 for all four survival endpoints), but we found significant interactions between tumor subtype and nodal stage (p < 0.05 for all four survival endpoints), with no differences in survival among tumor subtypes for patients with pN0 tumors (all p > 0.05) and pronounced differences in survival among tumor subtypes for patients with positive nodal stage (all p < 0.001)., Conclusions: This analysis confirms tumor size, nodal stage and tumor subtype as independent prognostic factors in high-risk early breast cancer. Nodal-positive patients with TNBC had a considerably worse outcome compared to nodal-positive patients with another tumor subtype. This underlines the importance for early detection particularly for patients with TNBC., Trial Registration: EudraCT 2005-000490-21; ClinicalTrials.gov Identifier: NCT02181101., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA)27.29 and circulating tumor cell (CTC) levels during therapy., Patients and Methods: A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy., Results: Overall, 1324 of the 2646 patients (50.0%) available for analysis had ≥ 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (χ 2  = 30.6, df = 3; P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test; Z = -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (χ 2  = 1.2, df = 3; P = .75)., Conclusion: Cautious interpretation is needed regarding elevated levels of MUC-1-derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial., Patients and Methods: The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (≥ 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses., Results: Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by ≥ 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067)., Conclusion: Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The second-to-forth digit length ratio (2D:4D) is considered to be a biomarker for intrauterine androgen levels. It is associated with adult and child mental health problems, primarily with behavioral symptoms and predominantly in males. Using a cross-sectional design, we examined whether 2D:4D was associated with conduct disorder (CD) symptoms in 138 primary-school aged children (54% boys, M age  = 7.70 years) and considered child sex as a moderating factor. Children's digit lengths were measured from hand scans and mothers rated the behavioral/emotional symptoms of their child. The regression analyses revealed that 2D:4D ratios were associated with behavioral symptoms in boys (β = -0.260, p = 0.026), but not in girls (β = -0.040, p = 0.762). Child emotional symptoms, analyzed as a control, were not significantly correlated with 2D:4D. In conclusion, prenatal brain hyperandrogenization - operationalized by the 2D:4D biomarker - could result in behavioral symptoms in boys at early school age, reflecting one predictor for early onset CD. Our data support the use of 2D:4D as a marker of prenatal androgen exposure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC)., Methods: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed., Results: This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern., Conclusions: This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Fertility-preserving measures are becoming important for patients receiving oncological treatment. One method involves cryopreservation of ovarian tissue and transplanting it when treatment is completed. We report complications resulting from surgical and fertility medicine, and the results of procedures for the removal and transplantation of ovarian tissue carried out within the FertiProtekt network. A survey using a structured questionnaire was conducted among the FertiProtekt network centres between November 2015 and June 2016. The analysis included surgical techniques used to remove and transplant ovarian tissue, surgical complications and results. Laparoscopic removal and transplantation of ovarian tissue have a low risk of complications. Surgical complications occurred in three of the network's 1373 ovarian tissue removals (n = 1302) and transplantations (n = 71); two complications (0.2%) occurred during removal and one during transplantation. Menstruation resumed in 47 out of 58 women (81%) who underwent ovarian tissue transplantation. Hormonal activity occurred in 63.2% of transplantations with a follow-up of 6 months or over. Sixteen pregnancies occurred in 14 patients, with nine births. The risks and complications of removal and transplantation of ovarian tissue are similar to those of standard laparoscopy. These procedures are becoming standard for fertility protection in cancer patients., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Preeclampsia is a hypertensive, gestational disease, which is still the leading cause of pregnancy related morbidity and mortality. The impairment of placental angiogenesis and vascularization is discussed to be of etiopathologic relevance. Deytrosination and tyrosination of α-tubulin is important for the stability and dynamics of microtubules. An increase of α-tubulin detyrosination leads to microtubule stabilization, which is an essential prerequisite for physiologic vascular tube morphogenesis during angiogenesis. So far, little is known about the specific localization of detyrosinated (detyr) and tyrosinated (tyr) tubulin in the placenta and its relevance for preeclampsia., Methods: Placental expression of detyr- and tyr-tubulin was analyzed by immunohistochemistry, immunofluorescence and western blot. For western blot quantification we used biopsies from healthy placentas (n = 21) and placentas from pregnancies complicated with small for gestational age (n = 5), preeclampsia (n = 5) or both (n = 5)., Results: Specific placental localization of detyr-tubulin was detected in the fetal endothelial cells of the placenta. Villous and extravillous trophoblasts as well as villous stroma cells were tyr-tubulin positive. Detyr-tubulin protein expression was significantly decreased in placentas complicated by preeclampsia., Conclusions: In summary, we report an accumulation of detyr-tubulin in villous vessels of the placenta and a significantly reduced level of detyr-tubulin in placental biopsies of preeclampsia cases. The reduction of placental detyr-tubulin in preeclampsia could suggest a deficit in villous vascular plasticity and might be associated with the impaired arborization of the disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life. Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL)., Materials and Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors., Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 - 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences., Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole., Patients and Methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT., Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit)., Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21)., Methods: We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA)., Results: Median age was 36 years (21-40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range < 0.1-11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to <0.1 ng/ml (range < 0.1-0.21 ng/ml). After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH <0.1 ng/ml, range < 0.1-3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients., Conclusions: In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC)., Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction., Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average., Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.

Objectives: Risk-reducing surgeries are a feasible option for mitigating the risk in individuals with inherited susceptibility to cancer, but are the procedures cost-effective in the current health-care system in Germany? This study compared the health-care costs for bilateral risk-reducing mastectomy (BRRM) and risk-reducing (bilateral) salpingo-oophorectomy (RRSO) with cancer treatment costs that could potentially be prevented., Patients and Methods: The analysis is based on interdisciplinary consultations with individuals with a high familial risk for breast and ovarian cancer at the University Breast Center for Franconia (Germany) between 2009 and 2013 (370 consultations; 44 patients with BRCA1 mutations and 26 with BRCA2 mutations). Health-care costs for risk-reducing surgeries in BRCA mutation carriers were calculated as reimbursements in the German diagnosis-related groups (DRG) hospital pricing system. These costs for the health-care system were compared with the potential cancer treatment costs that could possibly be prevented by risk-reducing surgeries., Results: Long-term health-care costs can be reduced by risk-reducing surgeries after genetic testing in BRCA mutation carriers. The health-care system in Germany would have saved € 136,295 if BRRM had been performed and € 791,653 if RRSO had been performed before the development of cancer in only 50% of the 70 mutation carriers seen in our center. Moreover, in patients with combined RRSO and BRRM (without breast reconstruction), one further life-year for a 40-year-old BRCA mutation carrier would cost € 2,183., Conclusion: Intensive care, including risk-reducing surgeries in BRCA mutation carriers, is cost-effective from the point of view of the health-care system in Germany., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cryopreservation of ovarian tissue has been successfully applied clinically, with over 60 live births to date. The aim of the present study was to perform a survey of patients who have had ovarian tissue cryopreserved in the Department of Obstetrics and Gynecology, Erlangen University Hospital, in order to obtain information about: why patients opt for fertility preservation; their current fertility; pregnancy attempts and outcomes; and their intended plans for the cryopreserved ovarian tissue. In total, 147 women took part in the survey (average age 25.0 ± 7.0 years; response rate 48%; mean follow-up period 6 years). Sixty-six reported regular menstrual cycles; 48 were amenorrhoeic. Sixty-two women had tried to conceive; 33 reported pregnancies. Twenty-five had delivered healthy children after conceiving naturally; eight had conceived with assisted reproduction. Five patients had had their ovarian tissue retransplanted. Although many patients continued to have ovarian function, none of them regretted choosing cryopreservation of ovarian tissue. Cryopreservation of ovarian tissue is an effective option and is very important for women diagnosed with cancer. Analyses of the clinical outcomes in these patients are essential in order to identify those patients capable of benefiting most from the procedure and in order to improve the technique., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Ovarian tissue preservation and retransplantation is a promising strategy to restore fertility in cancer survivors. Ischaemia accompanying ovarian tissue grafting, however, can lead to significant follicle loss. Transplantation of the whole ovary by vascular anastomosis has been considered as an alternative to prevent widespread ischaemic damage. In this study, the feasibility and function of transplanting whole ovary with intact vasculature were evaluated, with the goal of developing a xenograft model for studies using donated human ovaries. Whole-swine ovaries with vascular pedicles were perfused and transplanted as intact ovaries by anastomosis into irradiated ovariectomized nude rats (n = 10). The observation period was between 1 and 4 weeks. Fresh swine ovaries served as controls (n = 10). Ovarian stroma and follicle populations were assessed through histological examination in both transplanted and control ovaries. Most of the transplanted whole ovaries (n = 6) maintained stromal quality and all preantral follicle classes were represented, although follicle numbers decreased compared with fresh control. Four transplanted ovaries were fibrotic after 1-4 weeks within the nude rat. Our results demonstrate transplantation of whole-pig ovary into nude rats is possible and support development of this xenograft model system for human studies., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The murine placenta has a trichorial structure with two multinucleated syncytiotrophoblast (SCT) layers representing a barrier between the maternal and fetal blood system. Genes of endogenous retroviruses and retrotransposon-derived paternally expressed genes (Peg), remnants of past infections and integrations in the genome, have essential functions in placentogenesis. Previous studies showed that the envelope genes Syncytin-A and Syncytin-B were essential for cell-cell fusion of the SCT. The goal of this study was to analyze the temporal localization and expression of nine genes throughout placental development from embryonic day (E)8.5 to E18.5 using in situ-hybridization and absolute RNA-quantification. These included a comparison of previously characterized genes from the labyrinth Syncytin-A, Syncytin-B, Gcm1, the junctional zone PL-1, PL-2, Plf, Tpbpa with two further characterized genes Peg10 and Tpbpb. Syncytin-A and Syncytin-B RNA localized to SCT-I and SCT-II, respectively. Peg10 RNA localized to all extraembryonic tissues, specifically to the parietal and sinusoidal TGC of the labyrinth layer, which is in contact with SCT-I and the maternal blood. All three retroviral/retrotransposon-derived genes showed the highest expression at E16.5, but Peg10 with 188,917.1 molecules/ng cDNA was 208-fold and 106.8-fold higher expressed than Syncytin-A and Syncytin-B, respectively. Tpbpb localized to the junctional zone and showed the highest expression at E16.5 along with PL-2, Plf, Tpbpa, but not PL-1, which decreased in expression at E10.5. To investigate a role of Syncytin-A, Syncytin-B and Peg10 in cell-cell fusion, we established a cell culture system with fractionated primary trophoblasts from murine placentae. Culturing trophoblasts for up to 72h partly resembled trophoblast development in vivo according to the nine marker genes. Knockdown of Syncytin-A demonstrated a functional regulation of cell-cell fusion, where knockdown of Peg10 showed no involvement in cell fusion. Due to the expression of Peg10 in TGCs, we propose an essential functional role in the fetal-maternal blood system., (Copyright © 2013 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

The aetiology of anti-resorptive agent-induced osteonecrosis of the jaw (ARONJ) is still under debate. Clinical and genetic risk factors are currently being investigated to help understand its pathogenesis. This case-control study analysed a large number of cancer patients (n = 230) under therapy with intravenous bisphosphonates, half of which were diagnosed with ARONJ. Multiple myeloma, greater patient age and the use of more than one bisphosphonate were identified as clinical risk factors on logistic regression analysis. In addition, 204 patients were genotyped for HLA-DRB1 and DQB1 and the allele frequencies were compared between ARONJ (n = 94) and unaffected cancer patients (n = 110). For the HLA class II alleles, a strong increase in the frequency of DRB1*15, DQB1*06:02, DRB1*01 and DQB1*05:01 was observed in the ARONJ group. These results were reinforced on analysis of the respective haplotypes, with DRB1*15-DQB1*06:02 being significantly associated with the development of ARONJ (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0). The presence of at least one of the haplotypes DRB1*15-DQB1*06:02 and DRB1*01-DQB1*05:01 was highly associated with the development of ARONJ (OR 3.0; 95% CI 1.7-5.5). The data in this study of a large number of cancer patients receiving intravenous bisphosphonates suggest that MHC class II polymorphisms represent genetic risk factors for the development of ARONJ. This result supports recent findings that inflammation and infection might play an important role in the pathogenesis of ARONJ., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Cryopreservation of whole organs has become increasingly successful in recent years, and establishing reliable methods for confirming the success of specific cryopreservation procedures has therefore become extremely important. On the assumption that methods such as histological evaluation do not provide definitive evidence of long-term cryopreservation and that clear signs of conserved function in an organ are good evidence of its viability, contractile function was analysed in porcine uteri (n=60), either after long-term (group A) or short-term (group B) cryopreservation and post-thaw treatment with three different uterotonics. A slow freezing protocol was used to preserve the organs. Fifteen fresh uteri were analysed similarly for contractile function, which was evaluated by measuring intrauterine pressure after administration of oxytocin, prostaglandin E(1) (PGE(1)), and carbachol. After cryopreservation, all but three uteri (95%) showed rhythmic contractions similar to those in fresh uteri except for differences in the heights of contraction peaks, with lower contractions in PGE(1) subgroup B (P<0.05). With the exception of three nonresponsive uteri in group A, there were no differences in contractility between uteri after long-term cryopreservation and fresh uteri. The results of this study thus contribute to the debate on whether slow freezing or vitrification techniques are best for whole-organ cryopreservation. In summary, (1) preservation of muscular function in porcine uteri is feasible with a slow freezing protocol; (2) measurement of contractile function following administration of uterotonics is a useful method of confirming functionality; and (3) long-term cryopreservation does not significantly impair post-thaw contractibility in comparison with fresh uteri., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer (MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C). Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01-8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83-15.58). The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Re-operations after breast conserving surgery (BCS) are necessary, when specimen margins are not free of breast cancer cells. This study explored the accuracy of preoperative tumour size assessment and its influence on the rate of re-excisions and mastectomies., Methods: The study included 1591 patients with invasive breast cancer, who were planned for BCS. Patient, staging and tumor characteristics were evaluated concerning their influence on re-excision and mastectomy rates. Patient and tumor characteristics comprised histopathological tumour size, HER2 status, multifocality, in situ component, grading (G), nodal status and hormone receptor (HR) status. Staging characteristics included deviation from pathological tumour size as measured by clinical examination, sonography and mammography., Results: In 1316 patients (83%) sufficient treatment was possible with one operation. 275 patients (17%) had to undergo at least one further surgery as a result of positive specimen margins. In 138 patients (9%) mastectomy was ultimately necessary. In patients with a positive HER2 status, a larger tumour size, underestimation by ultrasound, an in situ component and multifocality, the risk for a re-operation was about doubled. Tumour size deviation in the mammogram or the clinical tumour size assessment did not have significant influence to the re-excision rates., Conclusion: Tumour size and accurate presurgical assessment of the tumour size itself are independent predictors for the need of a second surgery or even a mastectomy in patients for whom a primary BCS was planned., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human β-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer., Patients and Methods: A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks followed by four cycles of paclitaxel 175 mg/m(2) every 3 weeks (EC→T), or three cycles of epirubicin 150 mg/m(2) every 2 weeks followed by three cycles of paclitaxel 225 mg/m(2) every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (E(dd)→T(dd)→CMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of E(dd)→T(dd)→CMF compared with EC→T., Results: Estimated 3-year DFS was 75.8% with EC→T versus 78.8% with E(dd)→T(dd)→CMF [hazard ratio (HR) 1.14; P = 0.37] and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response [pathological complete response (pCR)] had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001)., Conclusion: Neoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.

To compare the effects of neurotropic and musculotropic spasmolytic drugs in isolated swine uterus specimens, 80 swine uteri were perfused using an established model for preserving a viable organ that responds to oxytocic hormones and spasmolytic drugs. An intrauterine catheter was used to record pressure changes. Following initiation of rhythmic uterine contractions and recording of spontaneous rhythmic contractions, spasmolytic drugs (butylscopolamine, atropine, denaverine, morphine, metamizole, pethidine and celandine) were administered at various concentrations. The musculotropic relaxant denaverine in particular showed significant results (P ≤ 0.05) for all dosages and parameters investigated. In terms of muscle physiology, musculotropic agents (denaverine and celandine) have clear advantages in comparison with neurotropic (butylscopolamine and atropine) or musculoneurotropic (morphine, metamizole and pethidine) spasmolytic drugs for inhibiting contractions. Experiments with pethidine (Dolantin) also showed promising results; with celandine (Paverysat), an initial increase in contractions was observed that may suggest ways of promoting rapid directed sperm transport. Denaverine and pethidine in particular may in the future be able to play an important role in improving the pregnancy rate after IVF., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: This 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial sub-study examined the effects of anastrozole and tamoxifen on bone mineral density (BMD) following 5 years of treatment., Patients and Methods: Lumbar spine and total hip BMD were assessed at years 6 and 7 in a total of 71 eligible patients. In total, 50 patients had evaluable data., Results: Following anastrozole treatment, the lumbar spine median BMD increased by 2.35% (P=0.04) and 4.02% (P=0.0004) at years 6 and 7, while total hip median BMD increased by 0.71% (P=0.3) and 0.5% (P=0.8). After tamoxifen treatment, lumbar spine median BMD decreased by 0.79% (P=0.2) and 0.30% (P=0.9) at years 6 and 7, while total hip median BMD decreased by 2.09% (P=0.0003) and 2.52% (P=0.0002). Patients with a normal BMD or who were osteopenic at 5 years did not become osteoporotic., Conclusions: Anastrozole treatment-related bone loss did not continue into the off-treatment follow-up period. The recovery in lumbar spine BMD and absence of further loss at the hip is consistent with the reduction in the annual rate of fracture observed after treatment cessation in the main ATAC trial., (© The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

The objective of the study was to examine the uterine contractions and the arterial perfusion pressure changes after application of oxytocin, endothelin 1, prostaglandins PGE(1), PGE(2) and PGF(2alpha), in order to identify the substance with the greatest intrauterine pressure (IUP)/intra-arterial pressure (IAP) ratio, which means the substance most suitable for inducing uterine contractility without raising the systemic vascular pressure. Increasing doses of oxytocin, endothelin 1, PGE(1), PGE(2) and PGF(2alpha) were applied as bolus injection through the uterine artery of perfused swine uteri and the intrauterine and intra-arterial pressure rises were recorded. All substances showed a significant cervicofundic pressure gradient and, with the exception of PGF(2alpha), the uterine peristalsis moved towards the cervix uteri. The perfusion pressure after application of oxytocin, PGE(1), PGE(2) and PGF(2alpha) reached a maximum value and started to decrease, whereas endothelin 1 caused a continuous increase in the perfusion pressure. Endothelin 1 showed the lowest IUP/IAP ratio and oxytocin the greatest. In conclusion, the IUP/IAP ratio provides a promising new parameter for the study of uterine contractility physiology. Besides oxytocin, PGE(2) and PGF(2alpha) emerged as the best candidate substances to improve uterine contractility without raising the intra-arterial pressure., (Copyright 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: The human placenta as part of the feto-placental unit may influence fetal endocrine systems and may therefore represent a very important link between intrauterine growth restriction (IUGR) and metabolic disorders in later life. We aimed to analyze the effect of sample origin on gene expression of placental factors potentially involved in fetal programming in IUGR versus appropriate for gestational age growth (AGA) to standardize sample collection procedure for a multicenter approach., Design: Placental gene expression of insulin-like growth factor-binding protein (IGFBP)-1, prolactin, corticotropin releasing hormone (CRH) and leptin was measured and compared between proximal, intermediate and peripheral region of the placenta in 22 IUGR (proven by anomalous placental Doppler velocimetry) and 19 AGA neonates., Results: Whereas no difference in gene expression was seen in the proximal portion, in the intermediate placental region mRNA expression of IGFBP-1 (p = 0.01), prolactin (p = 0.04), CRH (p = 0.01) and leptin (p = 0.04) was increased in IUGR samples compared to controls. At the placental periphery, gene expression of these placental transcripts showed a higher expression level in IUGR placentas without statistical significance, except for leptin (p = 0.03)., Conclusion: Placental sampling site seems to be relevant for detecting differences in gene expression between IUGR and AGA neonates., (Copyright 2009 Elsevier Ltd. All rights reserved.)

There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone <2.5 mIU/l and > or =2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone > or =2.5 mIU/l had a significantly higher body mass index (P = 0.003), higher fasting insulin concentrations (P = 0.02) and altered insulin resistance indices (P = 0.007), higher total testosterone (P = 0.009) and free androgen indices (P = 0.001) and decreased sex hormone-binding globulin concentrations (P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5 mIU/l. Generally, all of these parameters correlated significantly (P < 0.05) with thyroid-stimulating hormone only in women with thyroid-stimulating hormone > or =2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone > or =2.5 mIU/l had significantly altered endocrine and metabolic changes.

Introduction: The proliferation biomarker Ki-67 is a prognostic factor for breast cancer that has been investigated in several retrospective studies and a few prospective ones. The aims of the present study were to examine interactions between Ki-67 and other biomarkers in breast cancer patients and to assess the relationship of Ki-67 to histological grading., Patients and Methods: Patients with uniform immunohistochemical staining of Ki-67 by MIB-1 were identified from the database of the University Breast Center for Franconia. Data were available for 1232 of 2523 patients with invasive breast cancer who had been treated between 1998 and 2005. Ki-67 index was determined during routine work-up of the breast cancers by several surgical pathologists according to a standardized procedure. The Ki-67 proliferation index was correlated with hormone receptor status, HER2/neu status, age, tumor staging, and prognosis. In routine clinical practice, the grading was assessed according to Elston and Ellis, along with all other parameters., Results: Ki-67 proliferation index>or=20% was found to be associated with all of the prognostic factors that were tested. However, it also maintained statistical significance relative to poor overall survival in a multivariate Cox proportional hazards model (hazards ratio 1.81; 95% CI, 1.17-2.78). The hazards ratio for disease-free survival did not reach statistical significance (HR 1.41; 95% CI, 0.95-2.09; P=0.086). However, in both models the grade was not an independent prognostic factor., Conclusions: For routine clinical purposes, grading appears to add only limited information about the prognosis in comparison with Ki-67 expression. Further investigation of quality assurance for grading and of Ki-67 as a prognostic and predictive factor is warranted.

Aim: The aim of this study was to evaluate factors affecting the risk for reexcision following breast-conserving surgery. Positive tumor margins are critical for local disease control following surgery for breast cancer. Several factors, including tumor size, multifocality, and an extensive in situ component, may be associated with a higher rate of repeat operations due to positive margins. This study included mammographic density in the analysis., Methods: A total of 565 breast cancer patients were considered eligible for breast-conserving therapy after a core biopsy had confirmed malignancy. The patients' mammographic findings were reviewed, and mammographic density was documented in addition to the histopathological features of the lesions. Associations between these factors and the risk for a second operation were analyzed using the chi-squared test, and a model was developed for multivariate analysis., Results: At least one repeat operation was necessary in 121 patients (21.4%), and mastectomy was ultimately necessary in 54 patients (9.6%). Tumor size, multifocality, and the presence of an in situ component were identified as risk factors. A mammographic density of category 4 was associated with a need for further surgery (OR 3.2; 95% CI, 1.2-11)., Conclusions: Mammographic density is an additional risk factor for a second operation following breast-conserving procedures, and it may make radiographic and intraoperative localization of the tumor technically difficult. Using mammographic density to define a group of patients with a higher risk of reexcision might allow these patients to benefit from more sophisticated methods of localization and margin assessment.

Objective: Uterine benign leiomyomas result from proliferation of a single smooth-muscle cell and their growth is affected by steroid hormones via steroid hormone receptors. This investigation analyzed the +331G/A and the V600L single nucleotide polymorphisms in the progesterone receptor, and correlated their incidence with clinical and tumor parameters as well as disease risk., Study Design: Peripheral blood DNA was analyzed for the frequency of both progesterone receptor single nucleotide polymorphisms in 270 women with uterine leiomyomas compared with 163 control women without uterine leiomyomas., Results: No correlation was found for both single nucleotide polymorphisms or the risk for developing myoma; however, statistical significant associations were found for single nucleotide polymorphism genotypes with specific clinical and tumor characteristics, eg, endometriosis, number of live births, menstrual cycle disorder, and leiomyoma focality., Conclusion: Our findings support that specific genotypes in the progesterone receptor may be involved in tumor growth and metastasis but not in tumor initiation.

The aim of this survey was to evaluate correlates for the patient's desire for surgical improvement of the cosmetic outcome after the primary operation for breast cancer. A cross-sectional study was carried out in a single follow-up outpatient clinic using a questionnaire. Patients were asked to assess their degree of satisfaction with the cosmetic results of their primary surgery and to state if they would like to undergo a further breast surgery to improve the appearance. Patients' characteristics were correlated with this desire. After breast-conserving surgery, 21.6% of the patients stated that they desired surgical improvement, in comparison with 29.8% of the patients who underwent mastectomy. In the latter group, the desire for improvement remained constant up to 5years after the initial operation, whereas it declined in the group of patients after breast-conserving surgery. Furthermore, a younger age and the perception that the appearance negatively influences femininity, partnership or sexual life were associated with a desire for further surgery. Breast reconstruction after mastectomy can be discussed with the patients even after a long follow-up, especially when the appearance seems to influence partnership issues.

Background: We routinely perform free DIEP flap and fascia-muscle-sparing (fms) TRAM flap procedures using fibrin sealant to stabilise anastomosed vessels, thus avoiding some of the difficulties associated with microsurgical anastomoses., Methods: Women undergoing elective, autologous breast reconstruction with free DIEP flaps or fms-TRAM flaps between June 2004 and June 2007 in two Interdisciplinary Breast Centres were included in a retrospective chart review., Results: A total of 349 breast reconstructions were performed in 325 women. Of these, 201 (57.6%) were free DIEP flap procedures and 148 (42.4%) were fms-TRAM flap procedures. Average hospital stay was 9.8 days. Complete flap loss was seen in 3 cases (0.9%). Low rates of post-operative complications were observed., Conclusions: Microsurgical breast reconstruction using free DIEP flaps and fms-TRAM flaps, with fibrin sealant for stabilisation of microvascular anastomoses, provides good post-operative outcome featuring a low incidence of flap loss or other common post-operative complications.

Ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication, is classified into two distinct forms, early-onset and late-onset OHSS. Few risk factors have been established, but no association with ABO blood group antigens was known. From January 2000 to October 2007, 122 patients with known blood groups and the diagnosis of OHSS were hospitalized. OHSS classification, pregnancies, age and time of in-patient treatment were collated. Two control groups were established. One group comprised 177 patients treated for infertility without developing OHSS (treatment/no OHSS) and known blood groups. A second one consisted of 2289 obstetric and gynaecological patients (O/G). OHSS grade I, II or III was found in 20, 47 and 55 patients, respectively. The pregnancy rate was 50.8% and did not differ among the different OHSS grades. Blood group A was significantly more frequent and blood group O less frequent in patients with early-onset OHSS compared with the two control cohorts (P = 0.009 versus treatment/no OHSS; P = 0.001 versus O/G). The odds ratio for patients with blood group A versus O to develop early-onset OHSS was 2.169 and 2.262, respectively. No increased risk for late-onset OHSS was found. Blood group A may be associated with early-onset OHSS in Caucasians.

Many patients with a history of breast cancer (BC) will suffer from vasomotor symptoms, which can be induced or exacerbated by treatment with tamoxifen or aromatase inhibitors. The LIBERATE trial was designed as a randomized, double-blind, multicenter trial to demonstrate that tibolone 2.5mg/day (Livial) is non-inferior to placebo regarding BC recurrence in women with vasomotor symptoms surgically treated for primary BC within the last 5 years. Secondary objectives are effects on vasomotor symptoms as well as overall survival, bone mineral density and health-related quality of life. Mean age at randomization was 52.6 years, and the mean time since surgery was 2.1 years. The mean daily number of hot flushes and sweating episodes was 7.3 and 6.1, respectively. For the primary tumor, Stage IIA or higher was reported for >70% of the patients. In subjects whose receptor status was known, 78.2% of the tumors were estrogen receptors positive. At randomization, tamoxifen was given to 66.2% of all patients and aromatase inhibitors to 7%. Chemotherapy was reported by 5% at randomization. The adjuvant tamoxifen use in LIBERATE allows a comparison with the Stockholm trial (showing no risk of BC recurrence associated with hormone therapy), which was stopped prematurely subsequent to HABITS. The LIBERATE trial is the largest, ongoing, well-controlled study for treatment of vasomotor symptoms in BC patients.

Objective: The enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) converts cortisol into cortisone. Reduced placental activity of 11beta-HSD2 in small-for-gestational-age (SGA) neonates results in fetal cortisol excess. In the present study, we examined the yet unknown gene expression of 11beta-HSD1, which primarily synthesizes cortisol in SGA placenta., Study Design: In placentas taken from 24 women with normal-weight newborns and 16 women with SGA neonates, expression of 11beta-HSD1 and 11beta-HSD2 messenger ribonucleic acid (mRNA) was determined using reverse transcription-polymerase chain reaction., Results: Placental mRNA expression of 11beta-HSD1 and 11beta-HSD2 was significantly reduced in the SGA group (P = .006 and P < .0001). Both enzymes showed a significant correlation to birthweight SD score and placental weight. Also, levels of both enzymes were significantly correlated., Conclusion: In placental tissue of SGA neonates 11beta-HSD2 and 11beta-HSD1 gene expression is reduced. Adapted levels of 11beta-HSD1 might result in a counterregulatory mechanism limiting transplacental passage of elevated cortisol levels.

Objective: Assessment and adequate treatment of lymphedema is required by the European Society of Mastology. The purpose of our study was the evaluation of self-reported incidences of lymphedema in breast cancer survivors and the effect of providing the patients with information about lymphedema on the extent to which lymph-drainage massage services and compression garments were used., Methods: A total of 742 breast cancer survivors were analysed in this questionnaire-based survey. The associations between lymphedema and the patients' medical history; morbidity located in the breast, axilla, and arm; the amount of information the patients had received concerning lymphedema; and the extent to which lymph-drainage massage services and compression garments were analyzed., Results: 31.67% of the patients stated to have lymphedema. Radiotherapy was identified as a significant risk factor. Pain, paresthesia, and functional limitations were associated with the occurrence of lymphedema. The only independent positive predictive factor found to be associated with the use of lymph-drainage massage services (OR 5.74) was the provision of information about the condition., Conclusions: Self-reported assessment of lymphedema is feasible. The observed lymphedema incidence of approximately 30% may be able to serve as a basis for benchmarking in quality-assurance procedures at breast centers., Practice Implications: Control mechanisms are required to assess if the indication for lymphdrainage is adequate and the compliance to this subject is sufficient.

Aims: The aim of this study was to analyze patients' port-related quality of life., Patients and Methods: 260 consecutive patients with gynecological or breast malignancies were asked to take part in a questionnaire-based survey including 26 questions, and 232 women agreed to participate in the study. The questionnaire inquired about port-related aspects of everyday life and the use of a central venous access port device for chemotherapy and supportive cancer care. Multivariate analysis was used to identify parameters associated with satisfaction and dissatisfaction in relation to the port., Results: Most of the women were very satisfied with the use of a port to provide venous access for chemotherapy and supportive cancer care. Faster hospital procedures, good cosmetic results, and the ability to cope with the social environment had a significant influence on the degree of satisfaction. Fear of port punctures, inconvenient heparinization of the port, and fear of complications were found to be negative variables associated with the method., Conclusions: Port catheters are well accepted by patients for chemotherapy and supportive cancer care. Generally ports should be rapidly removed after the end of antineoplastic treatment in order to improve patients' satisfaction with the procedure.

Purpose: Because of the wide spectrum of indications and the different techniques used, amniotic membrane transplantation (AMT) may result in many variants of wound healing. Our aim was to investigate and classify the integration patterns of amniotic membrane (AM) into the human anterior cornea following AMT., Design: Retrospective, noncomparative, nonconsecutive, interventional case series., Participants: Twenty-four eyes of 24 patients (age, 64.9+/-13.6 years)., Methods: Eyes underwent penetrating keratoplasty 26.1+/-25.1 weeks (range, 0.3-79) after transplantation of cryopreserved human AM. Histopathologic and ultrastructural examinations were performed on the excised corneal buttons., Main Outcome Measures: Patterns were classified according to the topographic relationship between AM and corneal epithelium. The respective thicknesses of the corneal epithelium and AM layer(s) were measured., Results: Integrated AM was found in 18 of 24 corneas up to 79 weeks after transplantation. Amniotic epithelium was present in only 4 of 24 cases with intracellular signs of degeneration. Amniotic membrane stroma was integrated in 4 patterns: (1) intraepithelial (4 eyes); (2) subepithelial (11 eyes); (3) intrastromal, with various grades of retraction (4 eyes); and (4) superficial localization--AM present on the corneal surface (disintegration) (7 eyes). More than 1 pattern was found in 4 specimens. The thickness of corneal epithelium varied between 13.4 and 102.6 microm, and the thickness of AM between 9.0 and 162.5 microm., Conclusions: Amniotic membrane can integrate into the host corneal tissue after AMT in intraepithelial, subepithelial, or intrastromal patterns, or may be localized on the corneal surface. The thicknesses of corneal epithelium and AM are extremely variable. The morphology of the individual pattern seems to depend on the ocular surface disorder and AMT technique. Classification of AM integration patterns may assist in selecting the most suitable transplantation technique for specific surface disorders.

Study Objective: To evaluate the feasibility of total laparoscopic hysterectomy (TLH) using the Hohl instrument in an initial cohort of patients., Design: Retrospective cohort analysis (Canadian Task Force classification II-3)., Setting: Department of Obstetrics and Gynecology, Erlangen University Hospital, Erlangen, Germany., Patients: Forty-four women underwent the new TLH procedure using the Hohl instrument from May 2004 through January 2005. The laparoscopic approach was used when the patient had undergone more than one previous pelvic abdominal operation and/or had a reduced vaginal capacity. The indications for hysterectomy were symptomatic leiomyoma in 25 patients and hypermenorrhea in 19 patients., Intervention: Total laparoscopic hysterectomy using the Hohl instrument., Measurements and Main Results: No ureteral or bladder injury occurred in any of the patients. The complication rate during surgery and in the postoperative period was zero. The mean loss of hemoglobin was 1.68+/-0.96 g/dL, the mean operating time was 108+/-21 minutes, and the mean uterine weight was 302+/-121 g., Conclusion: Total laparoscopic hysterectomy using the Hohl instrument simplifies the surgical procedure. The reported technique is an option comparable with laparoscopic-assisted vaginal hysterectomy and may be effective in preventing minor and major complications during TLH.

Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case-control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia.

In bone scintigraphy, the differentiation between degenerative processes and bone metastases is still difficult. Therefore, additional radiological studies are regularly needed after bone scintigraphy. The now introduced hybrid-cameras combining single-photon emission computed tomography (SPECT) and spiral-CT are unique in the sense that they offer the opportunity to correlate the functional information with morphology in one session. We herein present two patients in whom this technological setup allowed a definite diagnosis in scintigraphically unclear vertebral lesions. In a patient with breast cancer, hypermetabolic lesions were clearly correlated with osteolyses. In another patient with synovial carcinoma, spondylosis and spondylarthrosis caused focal tracer uptake in the lumbar spine. In addition to an improved diagnostic accuracy, SPECT/Spiral-CT will considerably abbreviate the diagnostic process.