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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.)

Background: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses., Patients and Methods: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms., Results: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups., Conclusions: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients., Clinical Trial Number: NCT 00567554, www.clinicaltrials.gov., (© The Author 2014. 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: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival., Methods: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684., Findings: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1-5·1) for TARGIT versus 1·3% (0·7-2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1-4·2) versus 1·1% (0·5-2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0-9·7] vs EBRT 1·7% [0·6-4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5-4·3] for TARGIT vs 1·9% [1·1-3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8-2·5] vs 3·5% [2·3-5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7-5·8) for TARGIT versus 5·3% (3·9-7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029)., Interpretation: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT., Funding: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research., (Copyright © 2014 Vaidya et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.)

Background: After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy., Methods: Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective, randomised, non-inferiority trial, women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries. Patients were randomly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy. Neither patients nor investigators or their teams were masked to treatment assignment. Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy (in an expected 15% of patients). The primary outcome was local recurrence in the conserved breast. The predefined non-inferiority margin was an absolute difference of 2.5% in the primary endpoint. All randomised patients were included in the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00983684., Findings: 1113 patients were randomly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy. Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group, 854 (86%) received targeted intraoperative radiotherapy only and 142 (14%) received targeted intraoperative radiotherapy plus external beam radiotherapy. 1025 (92%) patients in the external beam radiotherapy group received the allocated treatment. At 4 years, there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20% (95% CI 0.53-2.71) in the targeted intraoperative radiotherapy and 0.95% (0.39-2.31) in the external beam radiotherapy group (difference between groups 0.25%, -1.04 to 1.54; p=0.41). The frequency of any complications and major toxicity was similar in the two groups (for major toxicity, targeted intraoperative radiotherapy, 37 [3.3%] of 1113 vs external beam radiotherapy, 44 [3.9%] of 1119; p=0.44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower in the targeted intraoperative radiotherapy group (six patients [0.5%]) than in the external beam radiotherapy group (23 patients [2.1%]; p=0.002)., Interpretation: For selected patients with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks., Funding: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research (BMBF)., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The purpose of this study was to assess mammographic and sonographic findings in a long-term follow-up (>or=3 years) after breast-conserving surgery (BCS) and IORT, either applied as boost or exclusively. Follow-up-findings of 54 patients were retrospectively evaluated and compared to a control group of 48 patients, treated with BCS and whole-breast radiotherapy. After IORT patients had a higher incidence of fat necroses manifesting as oil cysts in the late follow-up mammograms (n = 31 vs n = 8); furthermore, oil cysts were larger in the IORT group (median 4.5 vs 1.4 cm(2)). In 25 IORT patients the oil cysts arose from partially organized hematomas/seromas, which in this group were generally more frequent (n = 38 vs n = 9) and larger (median 3.6 vs 1.8 cm(2)). After IORT a decreasing incidence of hematomas/seromas was reciprocal to an increasing incidence of oil cysts, and the size of both entities correlated with each other. Liquid lesions with polypoid inner wall thickening on ultrasound, attributed to organized hematomas/seromas or fat necroses, appear more frequently after IORT (n = 15 vs n = 1). In conclusion, IORT is associated with a high incidence of large oil cysts, which arise from likewise large partially organized wound cavities. On ultrasound pronounced partial organization with polypoid inner wall thickening is a frequent finding in those cavities.

Background: Intraoperative radiotherapy (IORT) during breast-conserving surgery is increasingly used. We analyzed the influence of the interval between an IORT boost and external beam radiotherapy (EBRT) on late toxicity., Methods: Forty-eight patients received 20 Gy IORT (50 kV X-rays (Intrabeam, Carl Zeiss, Oberkochen, Germany) followed by 46-50 Gy EBRT with a median interval of 36 days (14-197). Late toxicity was assessed with the modified LENT SOMA score after a median of 36 months., Results: Twelve patients developed a higher grade fibrosis ( degrees II-III), three teleangiectases, one a breast edema grade degrees II, six retractions, four hyperpigmentations and five pain ( degrees II-III). The median interval between IORT and EBRT was significantly shorter in these patients (n=18) compared to the 30 patients without higher grade toxicity (29.5 days vs. 39.5 days, p=0.023, Mann-Whitney U-test)., Conclusion: Starting EBRT about 5-6 weeks after IORT appears to be associated with a decreased risk of chronic late toxicity compared with a shorter interval. The impact on local recurrence of prolonged gaps between IORT and EBRT is not known.

Objective: Human endometrium and early pregnancy decidua harbor a considerable and diverse population of antigen-presenting cells (APC). Changes in the number and distribution of macrophages and dendritic cells (DC) could point to a possible role of these immunocompetent cells in implantation and success of early pregnancy., Methods: Uterine tissue was obtained from 22 women undergoing hysterectomy for bleeding disorders or dysmenorrhea and from 11 women undergoing legal abortion. Tissue was investigated with antibodies against CD14, CD68, CD83, DC-SIGN, Ki-67, and human leukocyte antigen (HLA)-DR using single and double immunohistochemical staining techniques., Results: The number of CD14(+) cells was stable during all phases of the menstrual cycle and early pregnancy. In comparison to nonpregnant endometrium, DC-SIGN(+) cells showed a higher proliferation rate and were found associated in clusters with CD56(+) natural killer (NK) cells in early pregnancy. In the late secretory phase of the menstrual cycle, numbers of CD83(+) (P <.01) cells were significantly higher than in other endometrial phases and early pregnancy. HLA-DR(+) expression was significantly increased in early pregnancy but remained unchanged throughout the menstrual cycle., Conclusion: The presence of DC-SIGN(+) cells during the menstrual cycle and their proliferation in early pregnancy suggests an important role of these cells with regard to the balance between defense against pathogens and tolerance of the fetal allograft. Whether the increase of CD83(+) mature DC and CD68(+) macrophages in the late secretory phase is caused by hormonal stimuli and/or is due to changes of the cytokine/chemokine micromilieu remains to be investigated.

Objective: This study was undertaken to verify by means of Doppler ultrasonography and simultaneous fetal pulse oximetry the redistribution of fetal blood flow in favor of the brain during intrapartum hypoxemia., Study Design: During labor 11 term fetuses with abnormal heart rate patterns and arterial oxygen saturation <30% and 14 control term fetuses with normal oxygen saturation were simultaneously monitored by pulse oximetry and Doppler ultrasonography. The results were compared with the Student t test., Results: The blood flow velocity in the middle cerebral artery was significantly higher in the presence of reduced oxygen saturation, implying lower pulsatility and resistance indices (P <.001). The reduction of blood flow in the umbilical artery was not significant (P =.61)., Conclusion: Simultaneous intrapartum pulse oximetry and Doppler ultrasonography proved that reduced arterial oxygen saturation (<30%) is associated with profound changes in fetal hemodynamics and could be tolerated for only a limited period, which should be the subject of further studies.