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Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT.In a cohort of 11,982 BC patients diagnosed in 1998-2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events.Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94-1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98-1.01, P = .68).Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

Background The majority of breast cancer patients are severely psychologically affected by breast cancer diagnosis and subsequent therapeutic procedures. The COVID-19 pandemic and associated restrictions on public life have additionally caused significant psychological distress for much of the population. It is therefore plausible that breast cancer patients might be particularly susceptible to the additional psychological stress caused by the pandemic, increasing suffering. In this study we therefore aimed to assess the level of psychological distress currently experienced by a defined group of breast cancer patients in our breast cancer centre, compared to distress levels pre-COVID-19 pandemic. Methods Female breast cancer patients of all ages receiving either adjuvant, neoadjuvant, or palliative therapies were recruited for the study. All patients were screened for current or previous COVID-19 infection. The participants completed a self-designed COVID-19 pandemic questionnaire, the Stress and Coping Inventory (SCI), the National Comprehensive Cancer Network® (NCCN®) Distress Thermometer (DT), the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30, and the BR23. Results Eighty-two breast cancer patients were included. Therapy status and social demographic factors did not have a significant effect on the distress caused by the COVID-19 pandemic. The results of the DT pre and during COVID-19 pandemic did not differ significantly. Using the self-designed COVID-19 pandemic questionnaire, we detected three distinct subgroups demonstrating different levels of concerns in relation to SARS-CoV-2. The subgroup with the highest levels of concern reported significantly decreased life quality, related parameters and symptoms. Conclusions This monocentric study demonstrated that the COVID-19 pandemic significantly affected psychological health in a subpopulation of breast cancer patients. The application of a self-created “COVID-19 pandemic questionnaire” could potentially be used to help identify breast cancer patients who are susceptible to increased psychological distress due to the COVID-19 pandemic, and therefore may need additional intensive psychological support. Trial registration DRKS-ID: DRKS00022507. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-09012-y.

BACKGROUND/AIM There is a lack of data concerning the surgical treatment of locally advanced squamous cell carcinoma of the uterine cervix (LACC) with neoadjuvant and adjuvant chemotherapy (NACT, ACT) as well as total mesometrial resection (TMMR). The aim of the study was to present a novel approach for treating LACC using a tumor response score for NACT. PATIENTS AND METHODS A total of 12 patients with LACC were treated with NACT [cisplatin, ifosfamide, paclitaxel (TIP)], TMMR and ACT containing TIP. To measure the response during NACT, we scored i) the maximum tumor diameter (maxTD) in gynecological examination, ii) the MRI for radiologic maxTD, iii) the tumor volume and iv) the squamous cell carcinoma antigen before and after two applications of TIP. RESULTS TIP reduced all score-parameters in 10 of 12 patients (p

The psychological integration of body-related attitudes (BodyRA) is a critical developmental task in adolescence. Adolescents must adapt to their changing body image and body satisfaction. For young people, BodyRA (body dissatisfaction, bulimia, and drive for thinness) are connected to insecurities, which can disturb identity integration and personality development. Our goal was to evaluate the importance of BodyRA also for other mental disorders other than anorexia nervosa (AN), and the association between BodyRA with temperament and personality traits and identity diffusion. Data for the period of 2012 to 2019 were retrospectively analyzed from a convenience sample of patients in a child and adolescent psychiatric hospital (n = 114). The patients were 13 to 17 years of age and had a BMI of 11.9–36.1 kg/m2. As expected, BodyRA were found to be more pronounced in AN, as well as in borderline personality disorder (BPD), depression (DD), and attention deficit hyperactivity disorder (ADHD). BodyRA correlated significantly with internalizing problems in patients with DD (r = 0.428–0.565, p < 0.01) and BPD (r = 0.680, p < 0.01) as well as with BMI (r = 0.404, p < 0.01) in patients with DD. Moreover, we detected significant correlations with impaired identity development in patients with DD (r = 0.482–0.565, p < 0.01) and BPD (r = 0.681–0.703, p < 0.01). BodyRA also correlated significantly with the personality traits of harm avoidance (r = 0.377–0.541, p < 0.01) and self-directedness (r = −0.537–−0.635, p < 0.01) in DD. These personality traits and bulimia were used as predictors for identity diffusion in the investigated disorders of this study. We conclude that BodyRA, harm avoidance and self-directedness are associated with identity development in adolescent females with mental disorders.

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.

The onset of mental illness such as depression and anxiety disorders in pregnancy and postpartum period is common. The coronavirus induced disease 2019 (COVID-19) pandemic and the resulting public policy responses represent an exceptional situation worldwide and there are hints for adverse psychosocial impact, hence, the study of psychological effects of the pandemic in women during hospitalization for delivery and in the postpartum period is highly relevant.Patients who gave birth during the first wave of the COVID-19 pandemic in Germany (March to June 2020) at the Department of Obstetrics and Gynecology, University of Würzburg, Germany, were recruited at hospital admission for delivery. Biosamples were collected for analysis of SARS-CoV-2 infection and various stress hormones and interleukin-6 (IL-6). In addition to sociodemographic and medical obstetric data, survey questionnaires in relation to concerns about and fear of COVID-19, depression, stress, anxiety, loneliness, maternal self-efficacy and the mother-child bonding were administered at T1 (delivery stay) and T2 (3-6 months postpartum).In total, all 94 recruited patients had a moderate concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at T1 with a significant rise at T2. This concern correlated with low to low-medium general psychosocial stress levels and stress symptoms, and the women showed a significant increase of active coping from T1 to T2. Anxiety levels were low and the Edinburgh Postnatal Depression Scale showed a medium score of 5 with a significant (T1), but only week correlation with the concerns about SARS-CoV-2. In contrast to the overall good maternal bonding without correlation to SARS-CoV-2 concern, the maternal self-efficiency correlated negatively with the obstetric impairment caused by the COVID-19 pandemic.Obstetric patients` concerns regarding SARS-CoV-2 and the accompanying pandemic increased during the course of the pandemic correlating positively with stress and depression. Of note is the increase in active coping over time and the overall good mother-child-bonding. Maternal self-efficacy was affected in part by the restrictions of the pandemic. Clinical trial registration DRKS00022506.The global pandemic of COVID-19 (coronavirus induced disease 2019) is challenging our society in many ways. Especially pregnant women are facing extraordinary conditions and worries, like uncertain risks for mother and fetus in case of infection, restricted prenatal classes or restricted visitor regulations in hospitals. Particularly it is known that pregnancy and the postnatal period are presenting a more psychologically vulnerable time in a woman’s life. Developing the GeZeCO study, we aimed to focus on the pandemic’s effects on mental health of pregnant women during this time. Women giving birth in the department of obstetrics of the University Hospital Würzburg were asked to participate in the study. In total, 94 women completed several questionnaires concerning their mental health postpartum and again after 3 to 6 months. Further, we took blood samples of the women during the delivery stay and registered sociodemographic and obstetric data. Our results showed, that the women’s concern relating to COVID-19, as well as the level of depression and anxiety raised during the pandemic. In addition, the self-efficacy of the mothers was affected by the restriction measures. Despite this, the women had at large a good mother–child-bonding and their competence of active coping increased during time. In summary, we did find that the mental health of obstetric patients is impaired by the COVID-19 pandemic. This points out the importance of not only attending to physical health but also taking care of psychological stress and mental health problems of obstetric patients during this exceptional time.

Preeclampsia is characterized by maternal hypertension and multi-organ injury. Elongation factor Tu GTP binding domain containing 2 (EFTUD 2) and the Pregnancy Zone Protein (PZP) seem to be important immunomodulatory factors in early gestation. Little is known about the role of EFTUD2 and PZP in disorders of late pregnancy like preeclampsia, HELLP syndrome and intrauterine growth restriction (IUGR). PZP, EFTUD2 and hCG expression was investigated by immunohistochemistry in the placenta of healthy pregnancies (n = 13), preeclampsia (n = 11), HELLP syndrome (n = 12) and IUGR (n = 8). Correlation analysis of protein expression was performed via Spearman correlation coefficient. The characterization of EFTUD2 and PZP expressing cells was evaluated by double-immunofluorescence. After cultivation of the chorion carcinoma cell line BeWo with hCG the expression of PZP and EFTUD2 was investigated by immunocytochemistry. PZP expression was significantly downregulated in the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) of preeclampsia (ST: p 0.001, EVT:p = 0.019) and HELLP syndrome (ST: p = 0.004, EVT: p = 0.035). The expression of EFTUD2 was significantly lower in preeclampsia (ST: p = 0.003, EVT: p 0.001), HELLP syndrome (ST: p = 0.021, EVT: = 0.001, EVT: p = 0.001). EVTs were identified as EFTUD2 and PZP expressing cells by double-immunofluorescence. Stimulation of BeWo chorion carcinoma cells with hCG 1000 IU/mL for 48 h resulted in a significant upregulation of PZP expression (p = 0.027). Our results indicate that PZP and EFTUD2 might be involved in the development of placental dysfunction in preeclampsia and HELLP syndrome.

We aimed to explore the trajectory of financial difficulties among breast cancer survivors in the German health system and its association with migration background.In a multicentre prospective study, breast cancer survivors were approached four times (before surgery, before and after adjuvant therapy, five years after surgery) and asked about their migration history and financial difficulties. Migrants were defined as born/resided outside Germany or having citizenship/nationality other than German. Financial difficulties were ascertained with the financial difficulties item of the European Organisation for Research and Treatment of Cancer Core Instrument (EORTC QLQ-C30) at each time-point (cut-off 17). Financial difficulties were classified in trajectories: always (every time-point), never (no time-point), initial (first, not fourth), delayed (only fourth), and acquired (second and/or third, not first). A logistic regression was conducted with the trajectories of financial difficulties as outcome and migration background as exposure. Age, trends in partnership status, and educational level were considered as confounders.Of the 363 participants included, 49% reported financial difficulties at at least one time-point. Financial difficulties were reported always by 7% of the participants, initially by 5%, delayed by 10%, and acquired by 21%. Migrants were almost four times more likely to report delayed (odds ratio [OR] = 3.7; 95% confidence interval [CI] 1.3, 10.5) or acquired (OR = 3.6; 95% CI 1.6, 8.4) financial difficulties compared to non-migrant participants.Survivors with a migration background are more likely to suffer from financial difficulties, especially in later stages of the follow-up. A linguistically/culturally competent active enquiry about financial difficulties and information material regarding supporting services/insurances should be considered.

The implementation of patient blood management (PBM) is increasingly becoming standard in operative medicine. Recently, interest has also been shown for the vulnerable collective of pregnant women and neonates. As the information regarding anesthesiological procedures for pregnant women and the peripartum period including an informed consent process should be carried out long before childbirth, this provides a good possibility in this connection to incorporate PBM. An anesthesiological risk estimation as well as the diagnostic workup and treatment of potential anemia should be carried out during the pregnancy. Furthermore, loss of blood in anticipation of bleeding complications should be reduced by interdisciplinary preventive measures and an individually coordinated postpartum care should be organized. This results in an early diagnosis of anemia or iron deficiency with subsequent treatment also postpartum, analogous to the prepartum period.Die Implementierung eines Patient Blood Management (PBM) wird zunehmender Standard in der operativen Medizin. Seit einiger Zeit gilt das Interesse auch den vulnerablen Kollektiven der Schwangeren und Neugeborenen. Da die anästhesiologische Aufklärung der Schwangeren schon weit vor der Entbindung stattfinden soll, bietet sich in diesem Zusammenhang eine gute Möglichkeit, das PBM einzubinden. Bereits während der Schwangerschaft sollten eine anästhesiologische Risikoeinschätzung sowie die Abklärung und Therapie einer potenziellen Anämie erfolgen. Des Weiteren sollen Blutverluste in Antizipation von Blutungskomplikationen durch interdisziplinäre Präventivmaßnahmen reduziert und eine individuell abgestimmte postpartale Betreuung organisiert werden. Daraus resultiert analog zur Schwangerschaft auch postpartal die frühzeitige Erkennung einer Anämie oder eines Eisenmangels mit resultierender Therapiemöglichkeit.

Postpartum hemorrhage (PPH) nowadays still represents a severe complication of both a vaginal delivery and a cesarean section. In German-speaking areas a new definition of the term has recently become established and the nomenclature with respect to the severe form of PPH was dropped. The handling of misoprostol as a uterotonic during treatment of PPH is also new, which is available in Germany only as a medical direct import. For adequate diagnostics and targeted treatment interdisciplinary and standardized algorithms should be established and the specialist disciplines involved should be sensitized to this problem. In addition to an adequate hemostasis, a developing coagulopathy must be recognized at an early stage and treated with targeted coagulation management. Through implementation concepts, particularly the second pillar (minimization of blood loss) and the third pillar (rational use of blood transfusions) of patient blood management, various aspects for improvement of treatment of a PPH can be identified.Die postpartale Hämorrhagie (PPH) stellt bis heute eine schwerwiegende Komplikation, sowohl einer vaginalen Entbindung als auch einer Sectio caesarea dar. Im deutschsprachigen Raum hat sich in den letzten Jahren eine neue Definition des Begriffs etabliert, und die Nomenklatur bezüglich der schweren Form einer PPH wurde verlassen. Neu ist auch der Umgang mit Misoprostol als Uterotonikum im Rahmen der Therapie einer PPH, das seit Kurzem nur noch als ärztlicher Direktimport in Deutschland zur Verfügung steht. Für eine adäquate Diagnostik und zielgerichtete Therapie sollten interdisziplinäre und standardisierte Algorithmen etabliert sowie beteiligte Fachdisziplinen für diese Problematik sensibilisiert werden. Neben einer adäquaten Blutstillung muss auch eine sich entwickelnde Koagulopathie frühzeitig erkannt und durch ein zielgerichtetes Gerinnungsmanagement therapiert werden. Durch Implementierungskonzepte, insbesondere der 2. Säule (Minimierung von Blutverlusten) und 3. Säule (rationaler Einsatz von Blutkonserven) des Patient Blood Management (PBM), lassen sich verschiedene Aspekte zur Verbesserung der Therapie einer PPH identifizieren.

A 29-year-old woman suffered major traumatic brain injury caused by a car accident. As diagnostic measures had revealed an early pregnancy (9th week), treatment on the intensive care unit was continued for 5 months, after unfavourable cerebral prognosis was followed by an irreversible loss of brain function in the 10th week of pregnancy. After assisted vaginal delivery of a healthy child in the 31th week of pregnancy on the critical care unit, organ procurement took place according to the presumed will of the patient. The article presents the details of the critical care therapy and discusses the supportive medical measures. Those measures served primarily to uphold the pregnancy und support the healthy development and delivery of the fetus and only in second instance the organ preservation aiming on organ donation. Necessary measures included maintenance of vital functions, hemostasis of electrolytes, nutrition, treatment of infection, prevention of adverse effects on the fetus, substitution of hormones and vitamins as well as the preparation of a planned or an unplanned delivery.

The therapy of brain-dead pregnant women is an extreme example not only of the possibilities in current critical care, but also of resulting ethical, social and legal controversies, an area not familiar to most clinicians. Based on the case of a patient with fatal traumatic brain injury, a previously unknown early pregnancy and stated will to donate organs, we will discuss several aspects using published case reports: therapeutic goals, especially palliative care vs. continuation; implications of brain death diagnosis; considerations on legal care; involvement of relatives, especially the child's father; dynamics within the care team; and finally the issue of putative organ donation. This complex case once more depicts that even facing such highly unfavourable framework and seemingly irreconcilable factors, pregnancy can prevail. The researched facts and considerations in this article are intended to give an overview of potential dilemmas and might serve as a starting point in similar situations.Die Therapie Schwangerer mit irreversiblem Hirnfunktionsausfall ist ein Extrembeispiel nicht nur für die Möglichkeiten moderner Intensivmedizin, sondern auch für die daraus resultierenden ethischen, sozialen und rechtlichen Spannungsfelder, die für Mediziner kein vertrautes Terrain sind. Im Folgenden wird der Fall einer in der 9. SSW verunfallten Patientin mit infauster Prognose bei massivem Schädel-Hirn-Trauma und anamnestischem Wunsch zur Organspende vorgestellt. Vor diesem Hintergrund werden anhand ausgewählter Fälle aus der Literatur verschiedene Aspekte beleuchtet: die Frage der Therapiezielfestlegung, insbesondere Palliation vs. Fortführung; die Implikationen einer Hirntoddiagnostik; betreuungsrechtliche Überlegungen; Einbindung der Angehörigen, v. a. des Kindsvaters; Dynamiken im Behandlungsteam sowie schließlich die Frage einer möglichen Organspende. Das Fallbeispiel verdeutlicht zudem, dass auch bei denkbar ungünstigen Rahmenbedingungen und dem Zusammenkommen scheinbar unvereinbarer Faktoren eine Schwangerschaft überraschend unbeeinträchtigt ausgetragen werden kann. Die recherchierten Fakten und Erwägungen sowie die zitierte weiterführende Literatur in diesem Artikel sollen einen Überblick über potenzielle Dilemmata verschaffen und als fundierter Ausgangspunkt für ähnlich gelagerte Fälle dienen.

In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected.This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany.As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women.A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection.The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients.HINTERGRUND: Im Rahmen der Pandemie des SARS-CoV-2-Virus erlangte das Patientenkollektiv der Schwangeren früh Aufmerksamkeit. Initial wurde angesichts sich früh abzeichnender Krankheitsfälle bei jüngeren Patienten mit einem erheblichen Aufkommen peripartal zu betreuender, COVID-19-positiver Schwangerer gerechnet.Diese Arbeit vermittelt einen Einblick in die SARS-CoV-2-Infektionszahlen im Rahmen der geburtshilflichen Anästhesie zu Beginn der Pandemie sowie während der zweiten Infektionswelle in Deutschland.Über das COALA-Register (COVID-19 related Obstetric Anaesthesia Longitudinal Assessment-Registry) wurden sowohl von März bis Mai 2020 als auch von Oktober 2020 bis Februar 2021 in Deutschland und der Schweiz wöchentlich prospektiv Daten zu Verdachts- und bestätigten SARS-CoV-2-Fällen bei Schwangeren zum Zeitpunkt der Geburt erhoben. Betrachtet wurden die Verteilung dieser auf die Anzahl der Geburten, Zentren und Erhebungswochen sowie mütterliche Charakteristika und Krankheitsverläufe.Neun Zentren haben im Verlauf 44 SARS-CoV-2-positive Schwangere zum Zeitpunkt der Geburt bei 7167 Geburten (0,6 %) gemeldet (3 Fälle auf 2270 Geburten (0,4 %) und 41 Fälle auf 4897 Geburten (0,8 %)). Berichtet wurden 2 schwere COVID-19-Verläufe (n = 1 mit Todesfolge nach ECMO, n = 1 mit ECMO überlebt). Bei 28 (68 %) Patientinnen verlief die Infektion asymptomatisch. Ein Neugeborenes wurde im Verlauf positiv auf SARS-CoV‑2 getestet.Mithilfe des Registers konnte das Auftreten von Fällen zu Beginn der Pandemie zeitnah eingeschätzt werden. Es traten sporadisch Verdachtsfälle bzw. bestätigte Fälle auf. Aufgrund fehlender flächendeckender Testung muss aber von einer Dunkelziffer asymptomatischer Fälle ausgegangen werden. Während der zweiten Infektionswelle wurden 68 % asymptomatische Fälle gemeldet. Jedoch kann es bei jungen, gesunden Patientinnen ohne das Vorliegen typischer Risikofaktoren zu schwerwiegenden Verläufen kommen.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

Background This study examined the association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer. Patients and methods In the prospective multicenter cohort study BRENDA II, patients aged ≥65 years with primary breast cancer were sampled over a period of 4 years (2009-2012). A multiprofessional team (tumor board) discussed recommendation for adjuvant chemotherapy according to the German S3 guideline. Cognitive impairment was screened by the clock-drawing test (CDT) prior to adjuvant treatment. Results Two hundred and sixty-three patients were included in the study and CDT data were available for 193 patients. Thirty-one percent of the patients had cognitive impairment with different degree of severity. In high-risk patients (n = 61) tumor board recommendation in favor of chemotherapy was 90% and in intermediate-risk patients (n = 170) 27%. Not receiving recommendation for chemotherapy in spite of guideline recommendation was more frequent in patients with cognitive impairment (67%) vs patients without cognitive impairment (46%) with P = 0.02 (OR 2.4, 95% confidence interval (CI) 1.2-4.9). Age, education, migration background and comorbidities were not associated with chemotherapy recommendation by the tumor board among cognitively impaired patients. Once the tumor board had recommended chemotherapy, application of chemotherapy was similar in both groups of patients with or without cognitive impairment. Conclusion Almost one third of older patients with breast cancer are affected by cognitive impairment prior to adjuvant treatment. In these patients, cognitive impairment was associated with tumor board decision against chemotherapy in spite of a positive guideline recommendation.

Among patients with breast or gynecological cancer, supportive care needs are both highly prevalent and enduring. However, little is known about whether meeting patients' needs is accompanied by increased quality of life (QoL). We aimed to explore patients' supportive care needs reported at the beginning of inpatient rehabilitation and examined whether meeting these needs resulted in improved QoL.In a multicenter, prospective cohort study with 2 measurement occasions (beginning and end of inpatient rehabilitation), 292 patients with breast and gynecological cancer (mean age 55 years; 71% breast cancer) were enrolled. In 73%, time since diagnosis was longer than 6 months. We obtained self-reports of supportive care needs in 12 domains and measured QoL using the EORTC QLQ-C30 functioning subscales.At the beginning of inpatient rehabilitation, top-ranking severe supportive care needs concerned coordination of care (48%), medical information (45%), alleviation of physical symptoms (42%) and support with improving health behaviors (36%). At the end of inpatient rehabilitation, all needs assessed declined significantly, although many patients still expressed strong needs in some domains. However, meeting patients' needs was accompanied by improvements in all functioning subscales.This is the first study to show that meeting breast and gynecological cancer patients' supportive care needs during inpatient rehabilitation resulted in improved QoL. Given the considerable proportions of patients still reporting unmet needs at the end of their stay, stronger and continuing efforts seem warranted to meet these needs and thus further increase QoL.

This study examined 5-year overall, recurrence and distant metastasis-free survival (OS, RFS, MFS) of high- and intermediate-risk breast cancer (BC) patients who declined guideline-recommended adjuvant chemotherapy (CHT).In the prospective multicenter cohort study BRENDA II, patients with primary BC were sampled over a period of four years (2009-2012). A multi-professional team (tumorboard) discussed recommendation for adjuvant CHT according to the German guideline. Potential differences in 5 year survival were analyzed using Kaplan-Meier curves and Cox regression. The hazard ratios (HR) were adjusted for age, Charlson Comorbidity Score, American Society of Anesthesiologist (ASA) physical status classification, and endocrine therapy.A total of 759 patients were enrolled of which 688 could receive CHT according to the guidelines (n = 219 had a clear indication, in n = 304 it was possible). For 360 patients, the tumorboard advised to perform CHT, for 304 it advised against and in 24 cases, no decision was documented. Of those with a positive suggestion, 83% received CHT. Until 5 years after diagnosis, 57 patients were deceased, 41 had at least one distant metastasis and 29 a recurrence. There was no evidence for differences in OS and MFS in patients who declined CHT despite tumorboard recommendation (HR 3.5, 95% CI 0.8-15.1 for OS, HR 1.9, 95% 0.6-6.6 for MFS). Patients who received CHT had significantly better 5-year RFS compared to those who declined (HR 0.3, 95% CI 0.1-0.9, p = 0.03). There was no evidence for different survival in those who had no CHT because of comorbidity and those who declined actively, neither for OS, MFS nor RFS.The prospective BRENDA II study demonstrates benefit in RFS by guideline adherence in adjuvant breast cancer treatment, indicating prospectively the value of internationally validated guidelines in breast cancer care.

Reasonable to the improved prognosis of breast cancer (BC) long-term toxicities and side effects of oncological therapy gain more importance for work ability and social life of BC patients. Aim of this study was the analysis of occurence and differences of treatment-related side effects in relation to type of rehabilitation (so-called AHB vs. later rehabilitation) after therapy for BC.Clinical and patient related data as early and late toxicities after oncological treatment of 8.000 patients with BC (55.7±10.4y) were analyzed and compared with current literature.In 23.9% a mastectomy was performed, in 87.3% radiotherapy. In most cases an additional systemic treatment (57,6% CTX, 15,1% anti-Her2, 71% antihormonal treatment) was carried out. In 8.1% women suffered from recurrent or metastatic BC. As most common side effects of multimodal treatment weakness/fatigue (73,6%), insomnia (51,9%), CIPN (33%), lymph edema (13,9%) and drug-induced arthralgia (24,8%) were detected. In addition, 60.4% of women reported high levels of psychological distress. Shortly after therapy typical side effects were drug-induced toxicities (Leucopenia, p0.0001; anemia, p0.001; weakness/fatigue p0.001; CIPN, p0.0001), whereas in a later course chronic lymphedema (p0.0001), chronic or recurrent disease (p0.0001), status after mastectomy (p0.0001) and psychological distress (p0.0001) were significantly more often seen. Moreover, in this collective patients were significantly younger (53,7±9,8 vs. 56,3±10,7y).In BC patients, significantly different impairments and toxicities were documented between patients with early rehabilitation and patients with later onset of rehabilitation. These data may help to establish more individual and focused rehabilitation concepts in specialized centers.Infolge der zunehmend individualisierten, multimodalen Therapie gibt es eine Vielzahl von potenziellen, therapieinduzierten Folgestörungen bei Mammakarzinom-Patientinnen. Die zunehmend verbesserte Langzeitprognose, das häufig junge Erkrankungsalter und die hohe Inzidenz der Erkrankung unterstreichen die Bedeutung dieser teils chronischen Nebenwirkungen für die berufliche und soziale Teilhabe.Im Rahmen dieser retrospektiven Analyse wurden bei 8000 Brustkrebspatientinnen (Durchschnittsalter 55,7 ± 10,4J) klinische Parameter und therapieinduzierte Toxizitäten und Folgestörungen im zeitlichen Verlauf analysiert und mit Daten aus der Literatur verglichen.In 23,6% der Fälle wurde eine Mastektomie, in 89% eine Radiatio durchgeführt. Zudem erfolgte in den meisten eine zusätzliche systemische Therapie (57,6% CTX, 15,1% anti-Her2, 71% Antihormontherapie). In 8,1% lag ein Rezidiv bzw. eine metastasierte Erkrankung vor. Als häufigste Folgestörungen infolge der multimodalen Therapie ließen sich Kraftlosigkeit/Fatigue (73,6%), Schlafstörungen (51,9%), CIPN (33%), Lymphödeme (13,9%) und medikamentös-induzierte Arthralgien (24,8%) nachweisen. Zudem berichteten 60,4% der Frauen über einen hohen, psychischen Distress. Während kurz nach Akutbehandlung (AHB) signifikant häufiger CTX-induzierte Toxizitäten dokumentiert wurden (Leukopenie, p0,0001; Anämie, p0,001; Kraftlosigkeit/Fatigue p 0,0001; CIPN, p0,0001), ließ sich im Verlauf (REHA) häufiger ein chronisches Lymphödem (p0,0001), eine chronische Erkrankungssituation (p0,0001) sowie signifikant häufiger eine durchgeführte Ablatio (p0,0001) und psychischer Distress (p0,0001) nachweisen. Zudem zeigte sich ein jüngeres Alter (53,7±9,8 vs. 56,3±10,7J).Nach multimodaler Brustkrebstherapie lassen sich zwischen AHB- gegenüber Patientinnen im Regelheilverfahren teils signifikant unterschiedliche rehabilitationsrelevante Folgestörungen dokumentieren. Die Vielzahl und Vielfältigkeit somatischer sowie psychovegetativer Störungen unterstreichen die Notwendigkeit nach individualisierten, multimodalen Therapiekonzepten in der onkologischen Rehabilitation.

Background Pregnancy is an extraordinarily complex immunological process. For successful pregnancy maintenance the maternal immune system must adapt to and tolerate the semi-allogenic fetus at the fetomaternal interface of the placenta. This balance is regulated by cytokines with a predominant T helper 2 (Th-2) system and a suppressed inflammatory T helper 1 (Th-1) response. This study investigates the role of the Th-1 pro-inflammatory cytokine Interleukin-1 beta (IL-1β) and its role in early pregnancy loss. Patients and methods In order to identify differences in IL- β levels a TaqMan® Human Cytokine Network Array, with placental tissue obtained from patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15), was carried out. Protein expression of IL-1β in the decidua of healthy pregnancies (n = 15), spontaneous (n = 18) and recurrent miscarriages (n = 15), was investigated by immunohistochemistry. The identification of IL-1β expressing cells in the decidua was done with double-immunofluorescence. Results Gene expression analysis identified a nearly 54-times higher expression of IL-1β in placental tissue of patients suffering from recurrent abortion. Immunohistochemistry confirmed a significant upregulation of IL-1β in the decidua of recurrent miscarriage specimens (p = 0.01) as well as in the decidua of women with spontaneous abortion (p = 0.001). Double-immunofluorescence identified decidual stoma cells as IL-1β expressing cells. Conclusion Significant upregulation of IL-1β may be associated with an imbalanced immune system and a procoagulant state that could be responsible for early pregnancy loss. These results provide new evidence of the complex interplay of IL-1β at the fetomaternal interface and its crucial role in miscarriage processes.

Objective In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. Methods In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. Results There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (β 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (β − 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (β -0.34, p 0.03) and by immigrants (β -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (β 0.19/0.19/0.20/0.25; each p Conclusion Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Purpose Electrosurgery is the gold-standard procedure for the treatment of cervical dysplasia. The quality of the outcome depends on the accuracy of performance, which underlines the role of adequate training of surgeons, especially, as this procedure is often performed by novice surgeons. According to our knowledge, medical simulation has up until now lacked a model, which focuses on realistically simulating the treatment of cervical dysplasia with the concerning anatomy. Methods and result In our work, we present a model created using 3D printing for holistically simulating diagnostic, as well as surgical interventions of the cervix, as realistically as possible. Conclusion This novel simulator is compared to an existing model and both are evaluated. By doing so, we aim to provide novice gynecologists with standardized and high-quality simulation models for practicing to improve their proficiency.

Background Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care. Methods Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof-of-concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population-based Cancer Registry of Bavaria were linked at the district level. Results Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho-oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes. Conclusions Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high-quality health care to all inhabitants, regardless of residence.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been described as positively associated with cognitive functioning. Current meta-analyses have identified eicosapentaenoic acid (EPA) as potentially more effective than docosahexaenoic acid (DHA). An especially vulnerable subgroup that might benefit from these beneficial effects are depressed youths. In this study, we examined associations between red blood cell (RBC) DHA and EPA levels and depression severity and verbal memory performance in a sample of 107 moderately (n = 63) and severely (n = 44) depressed youths. The findings showed that youths with high RBC EPA levels had steeper learning curves compared to those with moderate or low RBC EPA levels (Pillai’s Trace = 0.195, p = 0.027, ηp2 = 0.097). No associations between RBC DHA levels or depression severity and verbal memory performance were observed. Our results further confirm previous findings indicating a more important role of EPA compared to DHA in relation to cognitive functioning. Future research should further investigate the differential role of EPA and DHA concerning cognitive functioning in depressed youths. Evidence supporting beneficial supplementation effects could potentially establish a recommendation for a natural and easily accessible intervention for cognitive improvement or remission., Nutrients, 12 (12), ISSN:2072-6643

Breast cancer is the most frequently diagnosed type of cancer in women and there are continuously new findings in research for further treatment approaches.Mammography is already a well-established prevention method in Germany for women aged 50-69, reducing mortality rates significantly. The benefit of extending the screening period including women older than 70 years has been proven recently. Intensive research in hereditary breast cancer makes it possible to identify high risk patients and include them to a more frequent screening program with additional MRI.In early as well as in advanced stages of breast cancer the treatment should be as targeted and as noninvasive as possible. After neoadjuvant therapy a mastectomy is needed less frequently and axillary lymph node dissection can be limited to rare cases. Molecular subtyping allows more individualized treatment in curative and palliative intention.BIA-ALCL is an uncommon and highly treatable T-cell lymphoma associated with textured silicone or saline filled breast implants. Despite increasing incidence the usage of those implants is possible - but only after adequate information.Due to new insights into the biology of breast cancer the period of follow-up care has been expanded to ten years.The detection of an ESR1 mutation could possibly be used as a predictive marker regarding endocrine therapy in the future. Furthermore, there are promising results for blocking the PD-1 axis in primary systemic chemotherapy for triple-negative breast cancer.VORSORGE, FRüHERKENNUNG UND FAMILIäRER BRUSTKREBS: Mit dem Mammografie-Screening für Frauen ab dem 50. Lebensjahr steht in Deutschland eine etablierte Früherkennungsmaßnahme zur Verfügung. Eine Reduktion der Mortalität ist gesichert. Das Screening kann mittlerweile auch bei Frauen über 70 fortgeführt werden. Durch intensive Forschung im Bereich des familiären Mammakarzinoms kann das Hochrisikopatientenkollektiv präziser bestimmt und einer intensivierten Früherkennung zugeführt werden. THERAPIE LOKAL BEGRENZTER STADIEN – SENKUNG DER RADIKALITäT: Die Behandlung erfolgt zielgerichtet und so wenig radikal wie möglich. Nach neoadjuvanter Chemotherapie kann immer öfter auf eine Brustamputation verzichtet werden. Die axilläre Lymphknotendissektion (ALND) bleibt wenigen Fällen vorbehalten. Die molekulare Subtypisierung ermöglicht individualisierte medikamentöse Therapien in der kurativen Absicht.Das BIA-ALCL stellt eine seltene Brustimplantat-assoziierte Erkrankung dar, bei der in den meisten Fällen eine Heilung möglich ist. Trotz steigender Inzidenz ist von Implantateinlagen nach adäquater Aufklärung der Patientin in Deutschland nicht abzuraten.Zur Behandlung des metastasierten Mammakarzinoms sollte wenn möglich eine gut verträgliche Therapie zur Erhaltung der Lebensqualität gewählt werden. Auch hier stehen immer mehr individualisierte Optionen zur Verfügung.Der Zeitraum der Nachsorge weitet sich aufgrund der Tumorbiologie auf 10 Jahre aus.Eine ESR1-Mutation kann zukünftig möglicherweise als prädiktiver Marker hinsichtlich einer antihormonellen Therapie in der Metastasierung genutzt werden. Für eine PD-1-Blockade gibt es vielversprechende Ergebnisse in der neoadjuvanten Behandlung des triple-negativen Mammakarzinoms (TNBC).

Background Pregnancy Zone Protein (PZP) is an immunosuppressive protein that is expressed by the placenta and has also been identified in immune cells. When PZP and Glycodelin A (GdA) are combined, they act synergistically to inhibit Th-1 immune response. Little is known about its combined expression and role in normal and disturbed first trimester pregnancy. Patients and methods We investigated the expression of PZP and GdA in placental tissue obtained from spontaneous miscarriage (SM) (n = 19) and recurrent miscarriage (RM) (n = 17) at gestational weeks 6–13 by immunohistochemistry and on mRNA-level by either TaqMan PCR or in situ hybridization. Placental tissue from legal terminations of healthy pregnancies (n = 15) served as control group. Immunofluorescence double staining was used to analyse the combined expression of PZP and GdA in decidual tissue. Results The protein level of PZP was significantly increased in decidual stroma of SM samples compared to the decidua of control specimens and also significantly upregulated in the decidual stroma cells in the RM group. Concerning GdA, the decidual stroma revealed a significantly decreased protein level in the group with spontaneous abortions than in the group with healthy pregnancies. There was also a significant downregulation of GdA in the decidual stroma of RM samples compared to the control group. We observed a significant negative correlation of PZP and GdA in decidual stromal tissue of recurrent abortion. We could confirm the staining results for PZP as well as for GdA on mRNA level. Both proteins are co-localized in decidual stroma as analysed by immunofluorescence double staining. Conclusion A balanced expression of GdA and its carrier protein PZP in the decidua seems crucial for a successful ongoing pregnancy. According to our data, these immunosuppressive proteins are co-localized in the decidual tissue and show a negative correlation only in patients suffering from recurrent abortion.

International audience; Background: The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood–brain barrier (BBB).Methods: We adapted and validated the CD34+ cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro.Results: The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment.Conclusion: We demonstrate that the CD34+ cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13

Background Elongation factor Tu GTP binding domain containing 2 (EFTUD2) is an alternative splicing factor that modulates cell differentiation and activation processes. EFTUD2 is known to modulate immune responses and mutation of the EFTUD2-gene lead to fetal malformation. Little is known about its expression and role in normal and disturbed first trimester pregnancy. Patients and methods We investigated the expression of EFTUD2 in placental tissue obtained from patients with normal (n = 14), spontaneous miscarriage (n = 15) and molar (n = 14) pregnancy by immunohistochemistry. The expression of EFTUD2 was correlated on the protein level with known immune modulatory proteins like pregnancy zone protein (PZP) and in addition with human chorionic gonadotropin (hCG). Furthermore, we analysed the EFTUD2 and PZP expression in vitro after stimulation of the chorioncarcinoma cell line JEG-3 with hCG. Results EFTUD2 is significantly upregulated in the syncytiotrophoblast of spontaneous miscarriage (p = 0.003) and molar pregnancy (p = 0.003) compared to week of gestation-adjusted normal first trimester placentas. PZP is negatively correlated (p = 0.021) to EFTUD2 in the syncytiotrophoblast and is therefore significantly downregulated in miscarriage (p = 0.028) and mole pregnancy (p = 0.006). In addition, hCG is positively correlated to EFTUD2 in mole pregnancy. The addition of hCG to chorioncarcinoma cell lines JEG-3 in vitro stimulated EFTUD2 expression in these cells (p = 0.027). Conclusion Regulation of alternative splicing seems crucial for a successful ongoing pregnancy. The up-regulated elongation factor EFTUD2 may have a critical role in miscarriage.

Purpose Robotic surgery represents the latest development in the field of minimally invasive surgery and offers many technical advantages. Despite the higher costs, this novel approach has been applied increasingly in gynecological surgery. Regarding the implementation of a new operative method; however, the most important factor to be aware of is patient safety. In this study, we describe our experience in implementing robotic surgery in a German University Hospital focusing on patient safety after 110 procedures. Methods We performed a retrospective analysis of 110 consecutive robotic procedures performed in the University Hospital of Würzburg between June 2017 and September 2019. During this time, 37 patients were treated for benign general gynecological conditions, 27 patients for gynecological malignancies, and 46 patients for urogynecological conditions. We evaluated patient safety through standardized assessment of intra- and postoperative complications, which were categorized according to the Clavien–Dindo classification. Results No complications were recorded in 90 (81.8%) operations. We observed Clavien–Dindo grade I complications in 8 (7.3%) cases, grade II complications in 5 (4.5%) cases, grade IIIa complications in 1 case (0.9%), and grade IIIb complications in 6 (5.5%) cases. No conversion to laparotomy or blood transfusion was needed. Conclusion Robotic surgery could be implemented for complex gynecological operations without relevant problems and was accompanied by low complication rates.

Certified multi-disciplinary breast cancer centres (CBCs) have been established worldwide. Development of CBCs, guideline-adherent systemic therapy and surgical management should now show an impact on outcomes. This analysis aimed to investigate whether guideline adherence (GA) rates, relapse-free survival (RFS) and overall survival (OS) have significantly improved at CBCs compared to the pre-certification period.8323 patients with primary breast cancer were treated in 17 German CBCs, which had been certified between 2003 and 2007 [2003 (n = 1), 2004 (n = 6), 2005 (n = 3), 2006 (n = 6) and 2007 (n = 1)]. 3544 patients (42.6%) were treated before certification and 4779 patients (57.4%) after certification.A highly significant (p 0.001) difference in 100%-GA was found between the various hospitals before certification (min 25.0%; max 54.6%). In 2008, when all participating hospitals were certified, the GA rate was 61.8% (min 39.5%, max 74.4%) and 69.2% (min 45.9%, max 86.4%) for patients75 y (n = 6675). The difference between pre-certification 100%-GA (46.9%) and post-certification (57.2%) was highly significant (p 0.001). RFS and OS were both significantly better after certification compared to the pre-certification period (RFS: HR = 0.79; 95% CI: 0.68-0.92; p = 0.003; OS: HR = 0.75; 95% CI: 0.65-0.85; p 0.001). 5-year RFS (OS) of patients75 y was 89.6% (85.4%) pre-certification and 91.4% (89.5%) post-certification. Since improvement in GA and outcomes correlated as well, GA remains a highly significant prognostic factor for RFS and OS regardless of NPI, intrinsic subtype and adjuvant systemic therapy. This suggests that the certification process is strongly associated with improvements in outcome.

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2 mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.

Background A successful pregnancy is a unique and complex immunological state. Cytokines seem to be crucial for the implementation of a tolerogenic environment at the feto-maternal interphase towards the semi-allogenic fetus. Importantly, the switch from a Th1- to a Th2 cytokine profile might play a key role. Interestingly, Interleukin-18 (IL-18) can induce either Th1 or Th2 immune response depending on the local cytokine environment. Therefore, this study investigates the expression of IL-18 in early pregnancy loss. Patients and Methods The TaqMan® Human Cytokine Network Array was carried out with placental tissue of patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15) in order to investigate differences in IL-18 mRNA expression. Immunohistochemical staining was applied to examine the IL-18 protein expression in the syncytiotrophoblast and decidua of healthy pregnancies (n = 15), spontaneous (n = 12) and recurrent miscarriage (n = 9). The characterization of IL-18 expressing cells in the decidua was evaluated by double-immunofluorescence. Correlation analysis between IL-18 protein expression and clinical data of the study population was performed via spearman correlation coefficient. Results Gene expression analysis revealed a 4,9-times higher expression of IL-18 in recurrent miscarriage patients. IL-18 protein expression was significantly upregulated only in the decidua in the recurrent miscarriage group (p = 0.031). We did not observe significant changes of IL-18 protein expression in spontaneous miscarriage specimens when compared to healthy controls (p = 0.172). Double-immunofluorescence identified decidual stroma cells as IL-18 expressing cells. Correlation analysis showed a significant negative correlation of IL-18 protein expression and gestational age in healthy controls (r = -,745, p = 0.034). Also, a positive correlation of IL-18 and maternal age was observed in patients suffering from recurrent pregnancy loss (r =, 894, p = 0.041). Conclusion Our results indicate that IL-18 expression might be necessary in early gestation but requires a tight regulation for a successful ongoing pregnancy. In the present study we observed that a significant upregulation of IL-18 in the decidua was restricted to patients with recurrent miscarriage and therefore might be interesting as a diagnostic marker. Further studies need to evaluate the exact pathophysiological mechanisms.

Objective: To identify subgroups of patients with pT1 pN0 breast cancer (BC) who might not profit from adjuvant systemic therapy (AST). Methods: Data of 3,774 pT1 pN0 BC patients from 17 certified BC centres within the BRENDA study group were collected between 1992 and 2008 and retrospectively analysed. Uni- and multivariate analyses were performed using Kaplan-Meier methods and Cox regression models. Results: 279 (7.4%) of the pT1 pN0 BC patients were T1a, 944 (25.0%) were T1b and 2,551 (67.6%) were T1c. There was no significant difference (p > 0.1) in recurrence-free survival (RFS)/overall survival (OAS) between patients with pT1a, pT1b, and T1c. Patients receiving any type of AST had a better outcome compared to women without AST after adjusting for age, tumour size, and intrinsic subtypes (RFS: p < 0.001; OAS: p < 0.001). AST was the most important prognostic parameter for RFS followed by intrinsic subtypes and age. Conclusion: Patients with pT1 pN0 BC profit from AST independently of molecular subtypes, tumour size, age or comorbidity, with 5-year RFS of more than 95%. The correct definition of subgroups of patients who do not need AST is still an open question.

In adults, anxious depression has been identified as a more severe form of major depressive disorder (MDD), associated with higher depression severity, more suicidal ideation and worse treatment outcome. Research in pediatric depression, however, has been sparse. 126 children and adolescents aged 8-18 years with a primary diagnosis of MDD were categorized into a MDD-only group and an anxious depression group based on clinically elevated scores on the Beck Anxiety Inventory. One-third of the sample was classified as having anxious depression with females being overrepresented in the anxious depressed compared to the MDD-only group. 42.2% of the anxious depressed youth met diagnostic criteria for a comorbid anxiety disorder. Anxious depressed youth were more likely to suffer recurrent depressive episodes, showed higher depression severity and a unique pattern of depressive symptoms characterized by more severe sleep problems, more somatic complaints, more severely depressed mood and more frequent suicidal ideations. Scores on a suicidal ideation scale were increased even when controlling for overall depression severity. However, when comparing depressed patients with and without comorbid anxiety disorders, no differences in depression severity, symptom patterns or suicidal ideations were observed. The results indicate that high anxiety levels in depressed youth are clinically relevant, and given the increase in suicidal ideation, anxiety symptoms during depressive episodes should routinely be screened in clinical practice even in the absence of a fully formed comorbid anxiety disorder.

Nectin‐2 is highly expressed in ovarian cancer. High expression of Nectin‐2 in ovarian cancer is associated with lymph node metastasis, residual tumor and poor prognosis. Nectin‐2 increases vascular permeability in ovarian cancer followed by ascites production. Nectin‐2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin‐2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin‐2 and CD31 using immunohistochemistry. Gene expression of Nectin‐2 was quantified by real‐time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin‐2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin‐2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin‐2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin‐2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin‐2 which was reversed by VEGF‐inhibition. In addition, Nectin‐2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin‐2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF‐induced Nectin‐2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production., publishedVersion

Background Breast cancer is the most common cancer in women. Diagnosis and treatment may drastically affect quality of life, causing symptoms such as sleep disorders, depression and anxiety. Mindfulness-based stress reduction (MBSR) is a programme that aims to reduce stress by developing mindfulness, meaning a non-judgmental, accepting moment-by-moment awareness. MBSR seems to benefit patients with mood disorders and chronic pain, and it may also benefit women with breast cancer. Objectives To assess the effects of mindfulness-based stress reduction (MBSR) in women diagnosed with breast cancer. Search methods In April 2018, we conducted a comprehensive electronic search for studies of MBSR in women with breast cancer, in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trial registries (World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov). We also handsearched relevant conference proceedings. Selection criteria Randomised clinical trials (RCTs) comparing MBSR versus no intervention in women with breast cancer. Data collection and analysis We used standard methodological procedures expected by Cochrane. Using a standardised data form, the review authors extracted data in duplicate on methodological quality, participants, interventions and outcomes of interest (quality of life, fatigue, depression, anxiety, quality of sleep, overall survival and adverse events). For outcomes assessed with the same instrument, we used the mean difference (MD) as a summary statistic for meta-analysis; for those assessed with different instruments, we used the standardised mean difference (SMD). The effect of MBSR was assessed in the short term (end of intervention), medium term (up to 6 months after intervention) and long term (up to 24 months after intervention). Main results Fourteen RCTs fulfilled our inclusion criteria, with most studies reporting that they included women with early breast cancer. Ten RCTs involving 1571 participants were eligible for meta-analysis, while four studies involving 185 participants did not report usable results. Queries to the authors of these four studies were unsuccessful. All studies were at high risk of performance and detection bias since participants could not be blinded, and only 3 of 14 studies were at low risk of selection bias. Eight of 10 studies included in the meta-analysis recruited participants with early breast cancer (the remaining 2 trials did not restrict inclusion to a certain cancer type). Most trials considered only women who had completed cancer treatment.MBSR may improve quality of life slightly at the end of the intervention (based on low-certainty evidence from three studies with a total of 339 participants) but may result in little to no difference up to 6 months (based on low-certainty evidence from three studies involving 428 participants). Long-term data on quality of life (up to two years after completing MBSR) were available for one study in 97 participants (MD 0.00 on questionnaire FACT-B, 95% CI -5.82 to 5.82; low-certainty evidence).In the short term, MBSR probably reduces fatigue (SMD -0.50, 95% CI -0.86 to -0.14; moderate-certainty evidence; 5 studies; 693 participants). It also probably slightly reduces anxiety (SMD -0.29, 95% CI -0.50 to -0.08; moderate-certainty evidence; 6 studies; 749 participants), and it reduces depression (SMD -0.54, 95% CI -0.86 to -0.22; high-certainty evidence; 6 studies; 745 participants). It probably slightly improves quality of sleep (SMD -0.38, 95% CI -0.79 to 0.04; moderate-certainty evidence; 4 studies; 475 participants). However, these confidence intervals (except for short-term depression) are compatible with both an improvement and little to no difference.In the medium term, MBSR probably results in little to no difference in medium-term fatigue (SMD -0.31, 95% CI -0.84 to 0.23; moderate-certainty evidence; 4 studies; 607 participants). The intervention probably slightly reduces anxiety (SMD -0.28, 95% CI -0.49 to -0.07; moderate-certainty evidence; 7 studies; 1094 participants), depression (SMD -0.32, 95% CI -0.58 to -0.06; moderate-certainty evidence; 7 studies; 1097 participants) and slightly improves quality of sleep (SMD -0.27, 95% CI -0.63 to 0.08; moderate-certainty evidence; 4 studies; 654 participants). However, these confidence intervals are compatible with both an improvement and little to no difference.In the long term, moderate-certainty evidence shows that MBSR probably results in little to no difference in anxiety (SMD -0.09, 95% CI -0.35 to 0.16; 2 studies; 360 participants) or depression (SMD -0.17, 95% CI -0.40 to 0.05; 2 studies; 352 participants). No long-term data were available for fatigue or quality of sleep.No study reported data on survival or adverse events. Authors' conclusions MBSR may improve quality of life slightly at the end of the intervention but may result in little to no difference later on. MBSR probably slightly reduces anxiety, depression and slightly improves quality of sleep at both the end of the intervention and up to six months later. A beneficial effect on fatigue was apparent at the end of the intervention but not up to six months later. Up to two years after the intervention, MBSR probably results in little to no difference in anxiety and depression; there were no data available for fatigue or quality of sleep.

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification., Ohio State University Comprehensive Cancer Center Barretos Cancer Hospital. Grant Number: FINEP ‐ CT‐INFRA (02/2010) Breast Cancer Foundation of New Zealand Canadian Institutes of Health Research. Grant Number: PSR‐SIIRI‐701 Cancer Research UK. Grant Numbers: C8197/A16565, C5047/A8384, C1281/A12014, C12292/A11174, C1287/A10710, C1287/A10118, C1287/A16563, C5047/A10692, C5047/A15007 Department of Defence, USA. Grant Number: W81XWH‐10‐1‐0341 Helsinki University Hospital Research fund Scientific Foundation Asociación Española Contra el Cáncer Leiden University Medical Centre. Grant Number: Grant 30.925 Generalitat de Catalunya. Grant Numbers: PERIS_MedPerCan, URDCat, 2017SGR1282, 2017SGR496 Royal Society of New Zealand Cancer Council Victoria Netherlands Organization for Scientific Research (NWO). Grant Number: Grant 017.008.022 Breast Cancer Research Foundation Cancer Foundation of Western Australia EU H2020. Grant Number: 634935 Fundación Mutua Madrileña Seventh Framework Programme. Grant Numbers: 634935, 223175, 633784 Cancer Council South Australia Government of Galicia. Grant Number: Consolidation and structuring program: IN607B Cancer Council Tasmania Italian Association of Cancer Research. Grant Number: 15547 Queensland Cancer Fund AstraZeneca National Institute of Health (USA). Grant Numbers: 1U19 CA148065‐01, CA128978, CA192393, 1U19 CA148537, P50 CA1162091, CA116167, 1U19 CA148112 Newcastle University Dutch Cancer Society KWF. Grant Numbers: KWF/Pink Ribbon‐11704, UL2012‐5649 National Institute for Health Research. Grant Number: Manchester Biomedical Research centre (IS‐BRC‐1215 National Council of Technological and Scientific Development (CNPq) Instituto de Salud Carlos III. Grant Numbers: FIS PI15/00355, FIS PI13/01711, CIBERONC, FIS PI16/01218, PI16/00563 French National Institute of Cancer National Breast Cancer Foundation National Health and Medical Research Council. Grant Numbers: ID1061778, ID1104808 Carlos III National Health Centro de Investigación Biomédica en Red de Enferemdades Raras. Grant Number: ACCI 2016: ER17P1AC7112/2018 Cancer Council NSW Deutsche Krebshilfe. Grant Numbers: (#110837, #70111850 Fondazione Pisa. Grant Number: Grant “Clinical characterization of BRCA 1/2 Mis

Background The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed? Methods A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines. Results 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy. Conclusion The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients.

BackgroundIn this study based on the BRENDA data, we investigated the impact of endocrine ± chemotherapy for luminal A, nodal positive breast cancer on recurrence free (RFS) and overall survival (OS). In addition, we analysed if tumor size of luminal A breast cancer influences survival in patients with the same number of positive lymph nodes.MethodsIn this retrospective multi-centre cohort study data of 1376 nodal-positive patients with primary diagnosis of luminal A breast cancer during 2001-2008 were analysed. The results were stratified by therapy and adjusted by age, tumor size and number of affected lymph nodes.ResultsIn our study population, patients had a good to excellent prognosis (5-year RFS: 91% and tumorspecific 5-year OS 96.5%). There was no significant difference in RFS stratified by patients with only endocrine therapy and with endocrine plus chemo-therapy. Patients with 1-3 affected lymph nodes had no significant differences in OS treated only with endocrine therapy or with endocrine plus chemotherapy, independent of tumor size. Patients with large tumors and more than 3 affected lymph nodes had a significant worse survival as compared to the small tumors. However, despite the worse prognosis of those, adjuvant chemotherapy failed in order to improve RFS.ConclusionsAccording to our data, nodal positive patients with luminal A breast cancer have, if any, a limited benefit of adjuvant chemotherapy. Tumor size and nodal status seem to be of prognostic value in terms of survival, however both tumor size as well as nodal status were not predictive for a benefit of adjuvant chemotherapy.

The development of metastases is the most aggressive attribute of breast cancer. In this retrospective multicenter study, we evaluated if and how the different pathological breast cancer subtypes influence the spreading of tumor cells, the development of metastasis and the survival of breast cancer patients. This retrospective German multicenter study is based on the BRENDA collective including 9625 breast cancer patients treated in the adjuvant setting. We used the χ 2 tests for the analysis of the categorical variables between groups of patients with different sites of metastasis. Survival distributions and median survival times were estimated using the Kaplan–Meier product-limit method. The log-rank test was applied to compare survival rates. The Cox proportional hazards model was used to estimate the hazard ratio and confidence intervals. 886 women developed metastases during a time interval of 53 months after primary diagnosis. Luminal A tumor patients were more likely to get bone metastases than lung, liver or CNS metastases. Patients with a triple-negative subtype were, however, the least affected by metastasis in the skeleton. They were most likely to develop visceral metastases. Location, numbers of metastases herein and the subtype influenced the overall survival (OAS). Altogether, the best OAS was found in patients with the luminal A subtype, the worst in patients with the triple-negative subtype. Knowledge of the typical metastatic pattern of the subtypes of breast cancer will help to personalize therapeutic options and follow-up examinations of cancer patients.

This study aims to answer the questions where breast cancer patients in Germany receive follow-up care (with what types of doctors) and what are the long-term problems and treatment regrets of breast cancer patients. In the prospective multicenter cohort study BRENDA II (“Breast Cancer under Evidence-Based Guidelines”), 456 patients with primary breast cancer were sampled consecutively over a period of 4 years (2009–2012) and contacted again 5 years after surgery. Long-term problems were elicited on a 4-point Likert scale ranging from 0 (‘not at all’) to 3 (‘very much’). 82% of the patients receive follow-up (FU) at the private practice gynecologist. In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner does this (multiple answers possible). Long-term problems attributed to the treatment were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94). Most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was most often for endocrine therapy (5%) and chemotherapy (4%). In Germany, different specialists are involved in the patients’ FU care for BC. The detection of long-term problems due to BC treatment is an essential part of FU care.

Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaβ ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.

To identify predictive ultrasound signs for unfavorable outcome in fetal gastroschisis (GS). This is a retrospective cohort study among pregnant women with the prenatal diagnosis of GS between 1998 and 2011 at the University of Wuerzburg, Germany. Analysis included prenatal ultrasound scans, neonatal intensive care unit (NICU) records, and pediatric records. The collected variables included maternal and fetal demographics, as well as an analysis of predictors for unfavorable fetal outcome. Unfavorable outcome was defined by more than 2 postnatal surgical interventions, intestinal resections, and long time to oral feeding (≥4 weeks). 35 cases of fetal GS were diagnosed, whereby 23 cases met the inclusion criteria and were evaluated by prenatal ultrasound and postnatal outcome. Based on the postnatal situation, 15 patients were classified in a good prognosis group and 8 patients in a poor prognosis group. Fetuses with poor prognosis were presented later during pregnancy (21.1 ± 6 vs. 26.9 ± 5.3 weeks; p

Treatment side effects, comorbidities, and guideline-adherent treatment (GL+) influence the oncologic outcome of older breast cancer patients (oBCP) (age ≥ 70 years). The focus of this analysis was to investigate the associations among tumor characteristics, guideline adherence, and outcome and to compare these associations between younger breast cancer patients (yBCP) (age 50-69 years) and oBCP.This is a retrospective multicenter cohort study with 17 participating certified breast cancer centers. The analysis of 10,897 patient records collected from 1992 to 2008 for GL+ and clinical outcome was performed. Tumor and patient characteristics and their associations with GL+ were compared between oBCP and yBCP.Nonguideline-adherent treatment (GL-) was associated with higher tumor stages and comorbidities. This effect was stronger in the oBCP group (P .001). GL+ was significantly more common in yBCP than in oBCP (P .001). The oBCP had significantly higher tumor stages, including tumor size (P .001), nodal status (P .001), and positive hormone receptors (P = .001). Tumor grading was lower (P = .001), and HER2neu overexpression was less frequent (P = .003) in oBCP. Overall survival and disease-free survival are significantly impaired if GL- occurred in patients with breast cancer independently of age.GL- is associated with decreased disease-free survival and overall survival in both age groups. GL+ decreases advanced tumor characteristics in all age groups but significantly more in oBCP. If patients received GL+, we were unable to detect a statistical significant difference in the survival parameters.

The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991–2000 (TI1) and 2001–2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100 % guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p

Purpose The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y): (1) Is there a significant difference in the distribution of the biological subtypes of oBCP vs younger breast cancer patients (yBCP; 50–69 y)? (2) Which biological subtype has the highest rate of non-guideline-adherent-treatment (GL−) among oBCP? (3) Is a single GL− (i.e. radiotherapy/surgery/endocrine-therapy/chemotherapy) significantly associated with the survival outcome in each biological subgroup? Methods Between 1992 and 2008 the BRENDA (‘BRENDA’ = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714). Results OBCP were more likely to have hormone receptor positive (HR+) and HER2 neu negative (HER2−) breast cancer (77.5% vs 74.5%). The rate of GL− was significantly different (p The survival parameters for HR+/HER2− and TNBC were significantly worse in case of GL− regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR−/HER2+ tumors for GL− for radiotherapy and in HR+/HER2+ tumors for chemotherapy. Conclusions Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP.

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Multimodal therapies affect the quality of life (QoL) of patients with primary breast cancer (PBC). The objectives of this prospective study were to explore the changes in QoL from diagnosis to conclusion of adjuvant therapy and to identify predictive factors of QoL. Before surgery (t1), before onset of adjuvant treatment (t2) and after completion of adjuvant chemo- or radiotherapy (t3), patients with PBC (n = 759) completed the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire, Charlson Comorbidity Index, Patient Health Questionnaire and Perceived Involvement in Care Scales. Predictors of the course of global QoL were estimated using multinomial logistic regression. Effect estimates are odds ratios (OR) and their 95% confidence intervals (CIs). Global QoL improved between t1 and t3, while physical functioning, emotional functioning and fatigue deteriorated. QoL before surgery was more often poor in patients

The diagnosis of extrauterine pregnancy is possible very early giving the patient and doctors treatment options. As the risks and success rate of medical and surgical treatment are similar, the decision is increasingly influenced by cost-effectiveness.The following article systematically reviews the known literature regarding cost, decision criteria and possible follow-up.Literature review of extrauterine gravity in combination with cost in the online National Library of Medicine since 1.1.1997 following the PRISMA recommendations.Six articles were identified in which the cost of the laparoscopic versus medical treatment is reviewed. In five articles, the medical treatment was shown to be more cost effective and in the sixth article the costs were found to be equal. The cost saving varies between 18 and 88% depending on the consideration of direct and indirect costs. If indirect expenses are considered, the total sum increases with treatment failures. Failure rates are given as up to 27% depending on the type of failure (surgical or medical). These rates seem to be linked indirectly with the β-HCG levels. Predictive parameters for the successful medical treatment are missing.The treatment of small extrauterine gravidities in haemodynamically stable patients (defined by HCG levels1,500 IU/l) is medically successful and cost-effective. With HCG levels between 1,500 IU/l and 3,000 IU/l, the treatment costs are similar. HCG levels5,000 IU/l favour the surgical treatment as being more cost-effective. A similar cut-off for the sonographic imaging is missing.

BACKGROUND Radiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients: 1. Does guideline-adherent RT improve primary breast cancer patient survival? 2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters? 3. Does adjuvant RT compensate for an incomplete tumor resection (R1)? PATIENTS AND METHODS In this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines. RESULTS The patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613]. CONCLUSION Our study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.