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Was ist neu? Risikofaktoren Hormonelles Ungleichgewicht, Gynäkomastie, Lifestyle-Faktoren und genetische Veränderungen (insbesondere BRCA2-Mutationen) zählen zu den Hauptrisikofaktoren für das Mammakarzinom beim Mann. Prognose Die Brustkrebserkrankungen von Männern gehen mit einer schlechteren Prognose einher als die der Frauen. Diagnostik Zur Abklärung eines suspekten Befunds in der männlichen Brust sollten nach Anamnese und klinischer Untersuchung eine Mammasonografie und Mammografie durchgeführt werden. Therapie Die Behandlung wird in enger Anlehnung an das Vorgehen bei der Brustkrebserkrankung der Frau durchgeführt. Es steht eine Vielzahl an medikamentösen Therapiemöglichkeiten zur Verfügung. Einige sind jedoch nur als Off-Label-Use anzuwenden, da eine Zulassung beim Mann fehlt. Nachsorge Die Nachsorge erfolgt nach einem standardisierten Nachsorgeschema analog dem weiblichen Mammakarzinom. Bei positiver Familienanamnese für das Mammakarzinom und/oder Ovarialkarzinom erfolgt die Beratung und Testung gemäß den Kriterien des Deutschen Konsortiums Familiärer Brust- und Eierstockkrebs.

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or – if evidence was lacking – on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Analysis of circulating cell-free DNA (ccfDNA) is a suitable tool for detecting somatic mutations for the purpose of making decisions on treatment, monitoring treatment response, and predicting survival. High-throughput techniques for ccfDNA extraction are essential to implementing ccfDNA testing in the clinical setting. We set out to compare two automated techniques with regard to hands-on time, ccfDNA output and integrity, and circulating mitochondrial DNA (mtDNA). CcfDNA was isolated using the EZ1&2 ccfDNA field test kit (EZ2 kit, QIAGEN) and the Maxwell RSC ccfDNA plasma kit (Maxwell kit, Promega). DNA was extracted from plasma of 30 breast cancer patients enrolled in the iMODE-B (#325_19B; 12.10.2020) study. Real-time PCR, fluorescence-based detection and automated electrophoresis were used to assess ccfDNA concentrations. The ccfDNA yield was significantly higher when extracted with the EZ2 kit. The EZ2 kit enabled the isolation of a higher proportion of short fragments and a lower proportion of long fragments, resulting in lower DNA integrity. Significantly lower mtDNA quantities were detected in the Maxwell eluate than in the EZ2 eluate. Thus, decisions on which extraction method to use should proceed on the basis of the required input for downstream applications, the anticipated fragment size and minimum hands-on time.

Objective This study aimed to provide an overview of the extent to which women with endometriosis are informed about, interested in, and make use of CAM, and to evaluate which of the methods are most often applied. Study Design A retrospective, two-center cohort study was conducted using a validated questionnaire among women with laparoscopically confirmed endometriosis at two urban teaching hospitals, certified as endometriosis centres. Results A total of 592 patients were included in the study and received the questionnaire; 114 (19.3 %) were included in the data analysis. Most of the women were not receiving hormone therapy at the time of the study (n = 60, 52.6 %). Most (n = 75, 65.8 %) were interested in CAM, but only a minority (n = 12, 10.5 %) had detailed knowledge about it. A total of 81 patients (71.1 %) had used at least one CAM method for disease management; the five most frequently used CAM methods were exercise (n = 55, 48.2 %), vitamins (n = 40, 35.1 %), yoga (n = 38, 33.3 %), homeopathy (n = 32, 28.1 %), and trace elements (n = 27, 23.7 %). Conclusions In our study population, women with endometriosis are strongly interested in using CAM, but have only limited information about it. Nevertheless, a majority of the patients had used at least one CAM method to relieve symptoms associated with the disease and the most often used was exercise.

Cell-in-cell (CIC) structures in breast cancer have so far been studied in a small inhomogeneous patient population, suggesting the prognostic importance of CIC. In the present study, we focused on CIC in early hormone-sensitive breast cancer. With in vitro co-culture experiments, we compared the homotypic phagocytic capacity of two breast cancer cell lines to that of primary human fibroblasts. Afterward, we studied 601 tissue specimens from 147 patients participating in an institutional accelerated partial breast irradiation (APBI) phase II trial. Both breast cancer cell lines performed non-professional phagocytosis at a higher rate than primary human fibroblasts. In this study cohort, 93.2% of the patients had T1 tumours, and 6.8% had T2 tumours. CIC was found in 61.2% of the patients, with a CIC rate ranging from

Simple Summary Accelerated partial breast irradiation represents a well-established and safe treatment alternative for selected patients with early stage breast cancer after breast-conserving surgery. In a prospective trial on external beam partial breast irradiation, the risk for radiogenic pneumonitis is analyzed. After a median follow-up of 56 (1–129) months, radiogenic pneumonitis grade 2 appeared in only 1/170 (0.6%) patients. Compared to standard whole breast irradiation, the radiation doses applied to the lungs were very low. The patient with the radiogenic pneumonitis was found to have a generally increased radiation susceptibility. Using accelerated partial breast irradiation, the risk of radiogenic pneumonitis appeared quite low and may be limited to very exceptional cases associated with innate risk factors with an increased radiation susceptibility. Abstract In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1–129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.

Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patientsʼ self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Background/Aims: Macromastia can cause physical and psychological problems. Conservative treatments such as physiotherapy and painkillers lead to substantial long-term costs, without any proven medical benefit. In contrast, surgical treatment with reduction mammoplasty leads to improvements in nearly all respects. This study analyzed the costs of reduction mammoplasty and calculated an incremental cost-utility ratio for the treatment. Patients and Methods: The data on 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative) as well as the patients’ files. Topics examined besides demographic data included physician visits, medical imaging, integrative medical procedures, remedial procedures, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before and after surgery. The data were used to calculate costs per year after surgical treatment for symptomatic macromastia. Costs of surgery, including the process of obtaining insurance reimbursement and postoperative complications, were taken into account to calculate the one-time costs of reduction mammoplasty. Results: The patients’ quality of life and satisfaction with the breasts improve after surgery. The one-time costs of reduction mammoplasty per patient amount to EUR 5,885, and the annual costs after surgery are EUR 200. The incremental cost-utility ratio for surgical treatments shows a saving of EUR 380 per quality-adjusted life-year (QALY) gained. Conclusions: These results show that reduction mammoplasty is a treatment that not only improves a patient’s quality of life but also saves money in the longer term in comparison with expensive and ineffective conservative treatment for macromastia.

Nahrungserganzungsmittel gewinnen immer mehr an Beliebtheit. Sowohl Patienten als auch gesunde Personen nehmen diese ein, um unter anderem eine Verbesserung der Lebensqualitat zu erreichen. Ob dies wirklich sinnhaftig ist, wird im Beitrag genauer untersucht. Ebenso wird eine genaue Ubersicht uber die Vitamine und die wichtigsten Spurenelemente gegeben. Mikronahrstoffe liefern dem Korper zwar keine Energie, mussen aber dennoch zugefuhrt werden. Am sinnvollsten ist es, alle notwendigen Vitamine und Spurenelemente uber die Nahrung aufzunehmen. Fur gesunde Personen mit einer ausgewogenen Ernahrung ist keine Supplementierung von Mikronahrstoffen notig. Allerdings ist bei Mangelzustanden, bei onkologischen Patienten, eine externe Zufuhr notwendig. Bei Krebspatienten sollte beispielsweise eine ausreichende Zufuhr an Vitamin C und D sichergestellt werden, falls notig auch uber Nahrungserganzungsmittel. Die aktuelle Datenlage zeigt, dass eine ubermasige Zufuhr aber teilweise sogar ins Gegenteil umschlagen kann. So wurde beispielsweise gezeigt, dass eine ubermasige Zufuhr von Vitamin B12 das Risiko fur ein Bronchialkarzinom erhohen kann. Ebenfalls kann aktuell aus onkologischer Sicht keine Empfehlung zur Supplementierung von Selen gegeben werden. Ein genauer Uberblick uber die aktuelle Datenlage wird im Artikel gegeben.

Purpose Second opinions in oncology are becoming increasingly important in an era of more complex treatments and a growing demand for information by patients. Therefore, we analyzed their effects and influencing factors like patients’ motives, subjective extent of information and satisfaction with communications. Methods This prospective study evaluated second opinions for patients with breast cancer or gynecological malignancy. The patients received a questionnaire before and two months after, which inquired expectations, reasons, and satisfaction with the second opinion and the attending physicians. Results A total of 164 patients were included and the majority had breast cancer (75.0%). Receiving the second opinion made 89.7% feel better informed, their need for information decreased (from 75.3% to 39.2%, P P = 0.0002). There were various reasons for requesting a second opinion, e.g., the extremely stressful situation of a cancer diagnosis, hope for change in the treatment recommendation or dissatisfaction with the initial physicians. Conclusions Second opinions can lead to significantly greater patient satisfaction, meeting the need for information and leading to better management of patients in the extremely stressful situation of a cancer diagnosis. Doctor–patient communications play a key role.

Oncological second opinions are becoming increasingly important given more complex treatment strategies, simultaneously more patients use complementary and alternative medicine (CAM), and many comprehensive cancer centers initiate integrative medicine programs. The present study focuses on analyzing the effects of a second opinion in relation to attitudes toward CAM.In this prospective study patients (n = 97) with a diagnosis of breast cancer or gynecological malignancies who had requested a second opinion received a questionnaire before and after the second opinion concerning their attitudes toward CAM.The majority of patients had breast cancer (72.2%, n = 70). Only 6.2% (n = 6) stated that they had been informed about CAM by the doctors who treated them first, 21.6% (n = 21) had received information about it when seeking the second opinion. After the first opinion, 42.3% (n = 41) wanted to try CAM, the same proportion trusted orthodox medicine alone. After the second opinion, 24 patients (24.7%) wanted to try CAM, while 38.1% (n = 37) relied exclusively on orthodox medicine. There was a significant correlation between an increased patients' need for information and interest in CAM (p = 0.02).Today, aspects of CAM still are very often no part of oncological first and second opinions. This might hence lead to discouraging patients to try out CAM and therefore integrative medicine programs in comprehensive cancer centers might be problem-solving.Hintergrund und Ziele: Im Zeitalter der komplexeren Krebstherapien gewinnt zum einen die onkologische Zweitmeinung zunehmend an Bedeutung, zum anderen nutzen immer mehr Patientinnen komplementäre und alternativmedizinische Verfahren und in vielen zertifizierten Onkologischen Zentren entstehen Sprechstunden für Komplementär- und Alternativmedizin. Eine Ana­lyse der Effekte einer onkologischen Zweitmeinung in Bezug auf die Einstellung zur Komplementär- und Alternativmedizin war somit Fokus der vorliegenden Studie. Patientinnen und Methoden: In der prospektiven Untersuchung wurden onkologische Zweitmeinungen evalu­iert. Patientinnen (n = 97) mit der Diagnose eines Mammakarzinoms oder eines gynäkologischen Malignoms erhielten vor und zwei Monate nach der onkologischen Zweitmeinung einen Fragebogen zu ihrer Einstellung zur Komplementär- und Alternativmedizin. Ergebnisse und Beobachtungen: Die Mehrheit der Patientinnen wies ein Mammakarzinom auf (72,2%, n = 70). Nur 6,2% (n = 6) der Patientinnen gaben an von den erstbehandelnden Ärzten bzw. 21,6 % (n = 21) im Rahmen der Zweitmeinung zur Komplementär- und Alternativmedizin informiert worden zu sein. Nach der Erstmeinung wollten 42,3% (n = 41) Komplementär- und Alternativmedizin ausprobieren und genau der gleiche Anteil vertraute nur auf Schulmedizin (42,3%, n = 41). Nach der Zweitmeinung wollten 24 Patientinnen (24,7%) Komplementär- und Alternativme­dizin ausprobieren, und 38,1% (n = 37) vertrauten aus­schließlich auf Schulmedizin. Es zeigte sich eine signifikante Korrelation zwischen einem erhöhten Informations-bedürfnis der Patientinnen und dem Interesse an Komplementär- und Alternativmedizin (p = 0,02). Schlussfolgerung: Im Rahmen der onkologischen Erst- oder Zweitmeinung wird auch heute noch in vielen Fällen nicht auf Aspekte der Komplementär- und Alternativmedizin ein­gegangen, was dazu führen kann, dass Patientinnen von der Komplementär- und Alternativmedizin Abstand neh­men. Der Aufbau von Sprechstunden für Komplementär- und Alternativmedizin in zertifizierten Onkologischen Zentren könnte hier hilfreich sein.

Background: In the German Mammography Screening Program, 62% of ductal carcinoma in situ (DCIS) and 38% of invasive breast cancers are associated with microcalcifications (MCs). Vacuum-assisted stereotactic breast biopsies are necessary to distinguish precancerous lesions from benign calcifications because mammographic discrimination is not possible. The aim of this study was to investigate if breast magnetic resonance imaging (MRM) could assist the evaluation of MCs and thus help reduce biopsy rates. Methods: In this IRB-approved study, 58 women (mean age 58 +/− 24 years) with 59 suspicious MC clusters in the MG were eligible for this prospective single-center trial. Additional breast magnetic resonance imaging (MRI) was conducted before biopsy. Results: The breast MRI showed a sensitivity of 86%, a specificity of 84%, a positive predictive value (PPV) of 75% and a negative predictive value (NPV) of 91% for the differentiation between benign and malignant in these 59 MCs found with MG. Breast MRI in addition to MG could increase the PPV from 36% to 75% compared to MG alone. The MRI examination led to nine additional suspicious classified lesions in the study cohort. A total of 55% (5/9) of them turned out to be malignant. A total of 32 of 59 (54 %) women with suspicious MCs and benign histology were classified as non-suspicious by MRI. Conclusion: An additionally performed breast MRI could have increased the diagnostic reliability in the assessment of MCs. Further, in our small cohort, a considerable number of malignant lesions without mammographically visible MCs were revealed.

Objective: The current study seeks to illustrate potential early and objective neurophysiological biomarkers of neurodegenerative cognitive decline by evaluating features of brain network physiological performance and structure utilizing different modalities.Methods: This study included 17 clinically healthy individuals with self-reported cognitive decline (Subjective Cognitive Decline group, SCD, no objective finding of cognitive decline), 12 individuals diagnosed with amnestic Mild Cognitive Impairment (aMCI), 11 individuals diagnosed with Dementia, and 15 healthy subjects. All subjects underwent computerized cognitive performance testing, MRI scans including T1 for gray matter (GM) volume quantification, DTI for quantification of white matter (WM) microstructure fractional anisotropy (FA) and mean diffusivity (MD), and brain network function evaluation using DELPHI (TMS-EEG) measures of connectivity, excitability, and plasticity.Results: Both DELPHI analysis of network function and DTI analysis detected a significant decrease in connectivity, excitability, and WM integrity in the SCD group compared to healthy control (HC) subjects; a significant decrease was also noted for aMCI and Dementia groups compared to HC. In contrast, no significant decrease was observed in GM volume in the SCD group compared to healthy norms, a significant GM volume decrease was observed only in objectively cognitively impaired aMCI subjects and in dementia subjects.Conclusions: This study results suggest that objective direct measures of brain network physiology and WM integrity may provide early-stage biomarkers of neurodegenerative-related changes in subjects that have not yet displayed any other objective measurable cognitive or GM volume deficits which may facilitate early preventive care for neurodegenerative decline and dementia.

Zusammenfassung Hintergrund Während einer Krebstherapie leiden viele Patienten an Mangelernährung oder Vitaminmangel. Die Behandlung nährstoffbezogener Mangelzustände sollte daher eine Ernährungstherapie und gegebenenfalls auch eine orale oder intravenöse Substitution von Mikronährstoffen beinhalten. Über Infusionstherapien mit mehreren Nährstoffen liegen nur wenige Informationen vor. Das Ziel dieser Studie bestand in der Entwicklung standardisierter Infusionsprotokolle für die Infusion von Mikronährstoffen im Rahmen der integrativen Medizin (IMed-Infusionen) und der Beschreibung von Nebenwirkungen der Behandlung und der Therapiezufriedenheit der Patientinnen. Methoden Für die IMed-Sprechstunde wurden in Zusammenarbeit mit der Apotheke des Universitätsklinikums Erlangen 4 spezielle Formulierungen für die intravenöse Anwendung entwickelt. Zwischen Oktober 2015 und Januar 2018 wurde eine retrospektive Querschnittsstudie durchgeführt, in der 45 Patientinnen mit gynäkologischen Krebserkrankungen oder Brustkrebs (BK) unter IMed-Infusionstherapie aufgenommen wurden. Von 20 Patientinnen wurden mithilfe eines standardisierten Fragebogens zu IMed-Infusionen Nachbeobachtungsdaten erhoben. Ergebnisse Während des Studienzeitraums wurden insgesamt 280 IMed-Infusionen verabreicht. Die meisten Patientinnen haben IMed-Regenerationsinfusionen erhalten (78 %). Die Patientinnen litten in der Mehrzahl der Fälle an BK und wurden mit Chemotherapie behandelt. Die meisten Patientinnen gaben ein hohes oder sehr hohes Maß an Zufriedenheit mit der Organisation (60 %), der allgemeinen Behandlung (65 %) und der Beratung (85 %) an. Über eine subjektive Besserung von krankheits- oder therapiebedingten Symptomen wie Fatigue, Polyneuropathie und Einschränkung der körperlichen Leistungsfähigkeit berichteten 70 % der Patientinnen, während 75 % eine subjektive Steigerung ihrer Lebensqualität angaben. Nebenwirkungen traten nur selten auf und waren leichter Natur. Schlussfolgerungen Die Therapie mit IMed-Infusionen bei Frauen mit BK oder gynäkologischen Krebserkrankungen muss denselben Standards genügen wie Arzneimitteltherapien. Obwohl es sich bei Vitaminen um Nahrungsergänzungsmittel handelt, sind eine gründliche Erhebung der Anamnese sowie eine angemessene Aufklärung der Patientinnen unerlässlich. Hierfür haben sich standardisierte Vorgehensweisen, wie im Rahmen der IMed-Sprechstunde der Fall, als hilfreich erwiesen.

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.

Background: The usefulness of clinical breast examination (CBE) in general and in breast cancer screening programs has been a matter of debate. This study investigated whether adding vision-impaired medical tactile examiners (MTEs) improves the predictiveness of CBE for suspicious lesions and analyzed the feasibility and acceptability of this approach. Methods: The prospective study included 104 patients. Physicians and MTEs performed CBEs, and mammography and ultrasound results were used as the gold standard. Sensitivity and specificity were calculated and logistic regression models were used to compare the predictive value of CBE by physicians alone, MTEs alone, and physicians and MTEs combined. Results: For CBEs by physicians alone, MTEs alone, and both combined, sensitivity was 71, 82, and 89% and specificity was 55, 45, and 35%, respectively. Using adjusted logistic regression models, the validated areas under the curve were 0.685, 0.692, and 0.710 (median bootstrapped p value (DeLong) = 0.381). Conclusion: The predictive value for a suspicious breast lesion in CBEs performed by MTEs in patients without prior surgery was similar to that of physician-conducted CBEs. Including MTEs in the CBE procedure in breast units thus appears feasible and could be a way of utilizing their skills.

This study is a retrospective chart review of 200 clients who participated in a non-verbal restorative cognitive remediation training (rCRT) program between 2012 and 2020. Each client participated in the program for about 16 weeks, and the study as a whole occurred over a five-year period. The program was applied to effect proper neural functional remodeling needed to support resilient, flexible, and adaptable behaviors after encountering a mild closed head traumatic brain injury (mTBI). The rCRT program focused on improving functional performance in executive cognitive control networks as defined by fMRI studies. All rCRT activities were delivered in a semi-game-like manner, incorporating a brain-computer interface (BCI) that provided in-the-moment neural network performance integrity metrics (nPIMs) used to adjust the level of play required to properly engage long-term potentiation (LTP) and long-term depression (LTD) network learning rules. This study reports on t-test and Reliable Change Index (RCI) changes found within individual cognitive abilities’ performance metrics derived from the Woodcock-Johnson Cognitive Abilities III Test. We compared pre- and post-scores from seven cognitive abilities considered dependent on executive cognitive control networks against seven non-executive control abilities. We observed significant improvements (p < 10-4) with large Cohen’s deffect sizes (0.78-1.20) across 13 of 14 cognitive ability domains with a medium effect size (0.49) on the remaining one. The mean percent change for the pooled trained domain was double that observed for the pooled untrained domain, at 17.2% versus 8.3%, respectively. To further adjust for practice effects, practice effect RCI values were computed and further supported the effectiveness of the rCRT (trained RCI 1.4-4.8; untrained RCI 0.­08-0.75).

Purpose Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. Methods A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. Results After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Conclusions Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC., Highlights • Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). • Results from a large BC cohort on the impact of percentage MD (PMD) on prognosis. • No association between PMD with disease-free and overall survival was found. • Risk stratification based on PMD seems not feasible for clinical routine.

Purpose Symptomatic macromastia causes physical and psychological problems that can lead to restrictions in the patients’ social and working lives and a reduced quality of life. Associated medical treatments also have a considerable impact on health-care costs. Several studies have assessed these costs, but the total disease costs of macromastia have never been evaluated on the basis of real-world data. Methods The data for 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative), as well as the patient files. Topics surveyed, besides demographic data, included physician visits, medical imaging, medical procedures, medical treatments, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before surgery, to calculate the costs per year of conservative treatment of symptomatic macromastia. Results The mean time from start of symptoms to surgery was 11.82 years. The data for this group of patients with symptomatic macromastia show that costs per patient amount to €1677.55 per year. These costs include medical consultation, radiological imaging, medical treatments and procedures, physical therapy and rehabilitation, medication, special brassieres, exercise classes costs for sick leave due to problems with macromastia, and travel expenses. Conclusions These results show that considerable health-care costs arise due to macromastia with conservative treatment. Overall, macromastia costs €1677.55 per patient/year. In particular, lost productivity due to sick days and the costs of physiotherapy are factors driving the high costs.

Purpose: Increasing numbers of breast cancer survivors have led to a growing demand for integrative medicine. When patients have completed treatments associated with severe side effects, attention turns to reducing psychological symptoms, coping behavior, and self-care. The aim of this study was to assess patient-reported benefits in relation to active participation, mind–body stabilization, and coping strategies in breast cancer patients receiving integrative medicine. Methods: In a cross-sectional study, health counseling and treatment provided by a standardized integrative medicine consultancy service at the University Breast Center of Franconia were evaluated in 75 breast cancer patients over a 15-month period. At the baseline, the patients answered a questionnaire on their medical history, symptoms, and the treatment goals they were hoping to achieve with integrative medicine. Patient-reported outcomes relative to active participation, mind–body stabilization, and coping strategies were analyzed. Results: A large majority of the patients had previous experience with integrative medicine (91%). Most reported that they achieved their treatment goals with integrative medicine. Ninety-one percent achieved active participation in cancer treatment, 90% mind–body stabilization, and 79% improvement in coping strategies. Besides active participation, which was greatest in patients with stable disease, the success of integrative therapy was independent of age, concomitant diseases, previous integrative medicine experience, treatment state, and systemic cancer therapy. Conclusion: Breast cancer patients benefit from the counseling and treatment provided with integrative medicine in mind–body stabilization and coping with cancer. Active participation in cancer treatment is important for the patients. Integrative treatment services should form part of routine patient care.

Purpose Despite patients’ widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals’ current implementation of it in clinical routine. A national survey was conducted to assess gynecologists’ attitudes to and implementation of complementary and integrative treatment approaches. Methods The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email. Results Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016). Conclusions There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

ObjectiveThe aim of this study was to evaluate brain white matter (WM) fibers connectivity damage in stroke and traumatic brain injury (TBI) subjects by direct electrophysiological imaging (DELPHI) that analyzes transcranial magnetic stimulation (TMS)-evoked potentials (TEPs).MethodsThe study included 123 participants, out of which 53 subjects with WM-related pathologies (39 stroke, 14 TBI) and 70 healthy age-related controls. All subjects underwent DELPHI brain network evaluations of TMS-electroencephalogram (EEG)-evoked potentials and diffusion tensor imaging (DTI) scans for quantification of WM microstructure fractional anisotropy (FA).ResultsDELPHI output measures show a significant difference between the healthy and stroke/TBI groups. A multidimensional approach was able to classify healthy from unhealthy with a balanced accuracy of 0.81 ± 0.02 and area under the curve (AUC) of 0.88 ± 0.01. Moreover, a multivariant regression model of DELPHI output measures achieved prediction of WM microstructure changes measured by FA with the highest correlations observed for fibers proximal to the stimulation area, such as frontal corpus callosum (r = 0.7 ± 0.02), anterior internal capsule (r = 0.7 ± 0.02), and fronto-occipital fasciculus (r = 0.65 ± 0.03).ConclusionThese results indicate that features of TMS-evoked response are correlated to WM microstructure changes observed in pathological conditions, such as stroke and TBI, and that a multidimensional approach combining these features in supervised learning methods serves as a strong indicator for abnormalities and changes in WM integrity.

Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Delayed identification of coagulopathy and bleeding increases the risk of organ failure and death in hospitalized patients. Timely and accurate identification of impaired coagulation at the point-of-care can proactively identify bleeding risk and guide resuscitation, resulting in improved outcomes for patients. We test the accuracy of a novel optical coagulation sensing approach, termed iCoagLab, for comprehensive whole blood coagulation profiling and investigate its diagnostic accuracy in identifying patients at elevated bleeding risk. Whole blood samples from patients (N = 270) undergoing conventional coagulation testing were measured using the iCoagLab device. Recalcified and kaolin-activated blood samples were loaded in disposable cartridges and time-varying intensity fluctuation of laser speckle patterns were measured to quantify the clot viscoelastic modulus during coagulation. Coagulation parameters including the reaction time (R), clot progression time (K), clot progression rate (α), and maximum clot strength (MA) were derived from clot viscoelasticity traces and compared with mechanical thromboelastography (TEG). In all patients, a good correlation between iCoagLab- and TEG-derived parameters was observed (p

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.

Introduction: Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. Methods: In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. Results: The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). Conclusions: Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.

The upper Cambrian Yancannia Formation is a small and isolated basement exposure situated in the southern Thomson Orogen, northwestern New South Wales. Understanding the geology of the Yancannia Formation is important, as it offers a rare glimpse of the composition and structure of the mostly covered basement rocks of the southern Thomson Orogen. It consists of deformed fine-grained, lithic-rich, turbiditic metasediments, suggesting deposition in a proximal, low-energy deep-marine environment. A 497 ± 13 Ma U–Pb detrital zircon date provides its maximum depositional age, the same as previously published for a tuff horizon in a correlative unit. Analysis of sedimentological, geochronological and geophysical data confirms the Yancannia Formation belongs to the Warratta Group. The Warratta Group exhibits many similarities to the Teltawongee Group in the adjacent Delamerian Orogen, including similar provenance, sedimentology and deep-water turbiditic depositional environment. Additionally, there is no sedimentological evidence for deposition of the Warratta Group following the ca 500 Ma Delamerian Orogeny, which suggests that the Warratta Group is syn-Delamerian. However, no geochronological or structural evidence for Delamerian orogenesis was observed in the Warratta Group, suggesting that the group was either unaffected by Delamerian orogenesis, or that no conclusive record remains. The provenance signature of the Warratta Group also bears strong similarities with the upper Cambrian Stawell Zone Saint Arnaud Group in the western Lachlan Orogen. Units east of Yancannia have similar provenance signatures to the Lower Ordovician Girilambone Group of the Lachlan Orogen, suggesting equivalents exist in the southern Thomson Orogen. These are likely to be the Thomson beds, deposited in a deep-marine setting outboard of the Delamerian continental margin. Structural analysis from a ∼10 km, semi-continuous, across-strike section indicates a major, kilometre-scale, upright, shallow northwest-trending, doubly plunging anticline dominates the Yancannia region. This D1 structure was associated with tight-to-isoclinal folding, penetrative cleavage and abundant quartz veining of probable Benambran age. Later dextral transpressional deformation (D2) produced a sporadic, weak cleavage and dextral faulting, possibly of Bindian age. Major south-directed thrusting (D3) on the adjacent Olepoloko Fault occurred in the early Carboniferous and appears to pre-date a later deformation event (D4), which was associated with kink folding.

ZusammenfassungIm Bereich der gynäkologischen Onkologie und Senologie gab es auch in diesem Jahr zahlreiche Publikationen und Kongressbeiträge, die Änderungen oder Ergänzungen zu bestehenden Therapiekonzepten mit sich bringen. Die personalisierte Medizin rückt weiter in den Fokus des allgemeinen Interesses und es findet eine Individualisierung der Therapieschemata statt, sodass Therapieentscheidungen nicht nur auf Grundlagen etablierter Charakteristika wie Tumorgröße und Nodalstatus basieren, sondern vielmehr molekularbiologische und genetische Eigenschaften zur Entscheidungsfindung hinzugenommen werden.Dabei werden entsprechende neue Therapiekonzepte nicht nur für Patientinnen mit vielfach vortherapierten, fortgeschrittenen und metastasierten Mammakarzinomen entwickelt, sondern sind Inhalt neoadjuvanter und adjuvanter Therapiestudien. Nach Jahren der Eskalation im Bereich der Therapieintensität und -dauer lässt sich zunehmend ein neuer Trend beobachten – die Überprüfung von Therapieschemata mit der Fragestellung, welche Patientinnen möglicherweise keinen Benefit bezüglich des rezidivfreien und des Gesamtüberlebens durch die Behandlung haben und bezüglich der Morbidität von einer Deeskalation einer Therapie profitieren.Traditionell zeigen sich im Bereich der gynäkologischen Onkologie weniger Neuerungen als im Bereich der Senologie. Im letzten Jahr hat sich jedoch auch hier einiges getan. So befassten sich jüngst publizierte Studien bezüglich des Ovarialkarzinoms nicht nur mit der Fragestellung, ob auch hier eine Deeskalation der operativen Therapie möglich ist, z. B. durch eine Selektionierung der Patientinnen nach Risikofaktoren und Verzicht auf eine Lymphonodektomie. Eine Studie zur sekundären, operativen Tumorlastreduktion bei Ovarialkarzinomrezidiv wurde ebenso publiziert wie eine Studie, die ein neoadjuvantes Therapiekonzept mit sekundärer operativer Tumorlastreduktion untersucht hat. Im Bereich der Systemtherapien kommen neben den selektiven PARP-Inhibitoren, die bereits beim platinsensiblen Ovarialkarzinomrezidiv zugelassen sind (Olaparib, Niraparib), weitere Studien zu späteren Therapielinien und zu Kombinationstherapien, beispielsweise mit Therapien aus dem Bereich der Immunonkologie (PD-L1-Antikörper).Beim Zervixkarzinom präsentieren neue Daten Möglichkeiten der Deeskalation des operativen Vorgehens beim frühen Zervixkarzinom mittels der pelvinen Sentinelnodebiopsie. Aktuell läuft eine weitere große internationale Studie, um die Daten zu validieren (SENTICOL III-Studie). Im Bereich der Immunonkologie wurden erste Daten zum Einsatz von PD-L1-Antikörpern beim fortgeschrittenen Zervixkarzinom berichtet.Bei Patientinnen mit einem fortgeschrittenen Endometriumkarzinom steht die Diskussion des Vorteiles einer postoperativen Radiatio versus einer Radiochemotherapie im Fokus laufender Studien.

Magmatic-textured zircon from medium- to high-K calc-alkaline Warraweena Volcanics (WV) in two drill holes have yielded concordant U–Pb dates of 417 ± 3.5 and 414 ± 4.0 Ma and are interpreted as ma...