689 results on '"Sara Y, Brucker"'
Search Results
52. Long-term effects of preeclampsia on maternal cardiovascular health and postpartum utilization of primary care: an observational claims data study
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Kathrin Haßdenteufel, Mitho Müller, Raphael Gutsfeld, Maren Goetz, Armin Bauer, Markus Wallwiener, Sara Y. Brucker, Stefanie Joos, Miriam Giovanna Colombo, Sabine Hawighorst-Knapstein, Ariane Chaudhuri, Gudula Kirtschig, Frauke Saalmann, and Stephanie Wallwiener
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Obstetrics and Gynecology ,General Medicine - Abstract
Purpose Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. Methods Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. Results The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). Conclusion Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account.
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- 2022
53. Non-invasive Chamber-Specific Identification of Cardiomyocytes in Differentiating Pluripotent Stem Cells
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Eva Brauchle, Anne Knopf, Hannah Bauer, Nian Shen, Sandra Linder, Michael G. Monaghan, Kornelia Ellwanger, Shannon L. Layland, Sara Y. Brucker, Ali Nsair, and Katja Schenke-Layland
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
One major obstacle to the application of stem cell-derived cardiomyocytes (CMs) for disease modeling and clinical therapies is the inability to identify the developmental stage of these cells without the need for genetic manipulation or utilization of exogenous markers. In this study, we demonstrate that Raman microspectroscopy can non-invasively identify embryonic stem cell (ESC)-derived chamber-specific CMs and monitor cell maturation. Using this marker-free approach, Raman peaks were identified for atrial and ventricular CMs, ESCs were successfully discriminated from their cardiac derivatives, a distinct phenotypic spectrum for ESC-derived CMs was confirmed, and unique spectral differences between fetal versus adult CMs were detected. The real-time identification and characterization of CMs, their progenitors, and subpopulations by Raman microspectroscopy strongly correlated to the phenotypical features of these cells. Due to its high molecular resolution, Raman microspectroscopy offers distinct analytical characterization for differentiating cardiovascular cell populations.
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- 2016
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54. Adressen
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Sara Y. Brucker, Elisabeth Simoes, Diethelm Wallwiener, Klaus Doubek, Anton Scharl, Karl Ulrich Bartz-Schmidt, Anil Batra, Annette Binder, Andreas L. Birkenfeld, Gerhard W. Eschweiler, Louise Fritsche, Meinrad Paul Gawaz, Alexandra Geffroy, Marek Glezerman, Joachim Graf, Eva-Maria Grischke, Ines Gruber, Peyman Hadji, Markus Hahn, Sabine Hahn, Bashar Haj Hamoud, Volker Heinecke, Jörg Henes, Melanie Henes, Alice Höller, Stephanie Hübner, Ingolf Juhasz-Böss, Jörg Keckstein, Marion Kiechle, Ludwig Kiesel, Ute Krainick-Strobel, Bernhard Krämer, Hildegard Kusicka, Barbara Lawrenz, Dorina Löffler, Alfred O. Mueck, Felix Neis, Katrin Neis, Klaus J. Neis, Patricia G. Oppelt, Ann-Christin Pecher, Constanza Anahí Pontones, Kristin Katharina Rall, Christl Reisenauer, Gaby Resmark, Norbert Schäffeler, Katharina Schlammerl, Barbara Schmalfeldt, Dorit Schöller, Erich Solomayer, Sahra Steinmacher, Thomas Strowitzki, Hanna Surmann, Elli Tavlaki, Eva J. Tegeler, Friederike Thomasius, Uwe Ulrich, Christina B. Walter, Anna-Lena Weingärtner, Isabella Wiesmeier, and Stephan Zipfel
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- 2023
55. Treatment strategies in patients with gynecological sarcoma : Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1)
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Eva Roser, Philipp Harter, Dario Zocholl, Dominik Denschlag, Radoslav Chekerov, Pauline Wimberger, Christian Kurzeder, Annette Hasenburg, Mustafa-Zelal Muallem, Alexander Mustea, Guenter Emons, A G Zeimet, Felix Beck, Tjadina Arndt, Sara Y Brucker, Stefan Kommoss, Florian Heitz, Julia Welz, Eva-Katharina Egger, Matthias Kalder, Paul Buderath, Maximilian Klar, Christian Marth, Uwe Andreas Ulrich, Michael Weigel, Lea Traub, Christoph Anthuber, Hans Strauss, Lars Hanker, Theresa Link, Karol Kubiak, Badrig Melekian, Daniela Hornung, Martin Pölcher, Bjoern Lampe, Thomas Krauß, Ulrich Keilholz, Anne Flörcken, Klaus Pietzner, and Jalid Sehouli
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Oncology ,Medizin ,Obstetrics and Gynecology - Abstract
ObjectiveGynecological sarcomas account for 3% of all gynecological malignancies and are associated with a poor prognosis. Due to the rarity and heterogeneity of gynecological sarcomas there is still no consensus on optimal therapeutic strategies. This study’s objective was to describe the treatment strategies used in patients with gynecological sarcomas in the primary course of disease.MethodsThe German prospective registry for gynecological sarcoma (REGSA) is the largest registry for gynecological sarcomas in Germany, Austria and Switzerland. Primary inclusion criteria for REGSA are histological diagnosis of sarcoma of the female genital tract, sarcoma of the breast or uterine smooth muscle tumors of uncertain malignant potential (STUMP). We evaluated data of the REGSA registry on therapeutic strategies used for primary treatment from August 2015 to February 2021.ResultsA total of 723 patients from 120 centers were included. Data on therapeutic strategies for primary treatment were available in 605 cases. Overall, 580 (95.9%) patients underwent primary surgery, 472 (81.4%) of whom underwent only hysterectomy. Morcellation was reported in 11.4% (n=54) of all hysterectomies. A total of 42.8% (n=202) had no further surgical interventions, whereas an additional salpingo-ophorectomy was performed in 54% (n=255) of patients. An additional lymphadenectomy was performed in 12.7% (n=60), an omentectomy in 9.5% (n=45) and intestinal resection in 6.1% (n=29) of all patients. Among 448 patients with available information, 21.4% (n=96) received chemo- or targeted therapies, more commonly as single-agent treatment than as drug combinations. Information about anti-hormonal treatment was available for 423 patients, among which 42 (9.9%) received anti-hormonal treatment, 23 (54.8%) of whom with low-grade endometrial stroma sarcomas. For radiotherapy, data of 437 patients were available, among which 29 (6.6%) patients underwent radiotherapy.ConclusionOur study showed that treatment of patients with gynecologic sarcomas is heterogeneous. Further trials are needed along with more information on treatment modalities, therapy response and patient-reported outcomes to implement new treatment strategies.
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- 2023
56. Kommunikation
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Sara Y. Brucker and Elisabeth Simoes
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- 2023
57. Frauengesundheit
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Sara Y. Brucker and Elisabeth Simoes
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- 2023
58. Kinder- und Jugendgynäkologie – die häufigsten Vorstellungsgründe
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Sahra Steinmacher, Andrina Kölle, Sara Y. Brucker, and Katharina Rall
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- 2021
59. Meeting Report: Third International Congress of the International Society of Uterus Transplantation, Tübingen
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Mats Brännström, Stefan G. Tullius, Jiri Fronek, and Sara Y. Brucker
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Transplantation ,Uterus ,Living Donors ,Humans ,COVID-19 ,Female ,Infertility, Female ,Pandemics - Abstract
Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. The International Society of Uterus Transplantation (ISUTx) was formally founded in 2017 and joined the Transplantation Society as a formal section in 2021. The Third International Congress of the ISUTx was held in Tübingen, Germany, in October 2021, as a hybrid meeting, attended virtually by about 450 delegates and in person by 35 delegates. This report summarizes the Tübingen meeting and complementary topics of relevance presented at the Second ISUTx state-of-the-art webinar meeting, held in Prague, in October 2020. Main topics covered included surgical considerations, including dissection of veins in living donors and the pros and cons of minimally invasive surgery; managing immune risks; UTx during the COVID-19 pandemic; lessons learnt in the areas of imaging and cytomegalovirus infection; long-term psychological outcomes; opportunities to increase organ availability; and new horizons in UTx, including potential reuse of transplants and the utilization of robotic approaches. Implementation of an International UTx Registry was discussed and considered crucial to assure quality, safety, and further progress in UTx. Attempts made thus far have been promising.
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- 2022
60. The Lack of Evidence for an Association between Cancer Biomarker Conversion Patterns and CTC-Status in Patients with Metastatic Breast Cancer
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Stefan Stefanovic, Thomas M. Deutsch, Sabine Riethdorf, Chiara Fischer, Andreas Hartkopf, Peter Sinn, Manuel Feisst, Klaus Pantel, Michael Golatta, Sara Y. Brucker, Marc Sütterlin, Andreas Schneeweiss, and Markus Wallwiener
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breast cancer ,intrinsic subtype ,biomarker conversion ,circulating tumor cells ,liquid biopsy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.
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- 2020
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61. Case report on rhabdomyolysis after minimally invasive surgery for squamous cell carcinoma of the uterine cervix and adhesions due to deep infiltrating endometriosis
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Sahra Steinmacher, Harald Abele, Sara Y. Brucker, and Florin-Andrei Taran
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Surgery ,RD1-811 ,Gynecology and obstetrics ,RG1-991 - Abstract
Rhabdomyolysis is a rare clinical condition resulting from severe muscle damage that can cause potentially life-threatening complications. Amongst other causes, muscle compression due to patient positioning during prolonged surgery may result in extensive skeletal muscle breakdown. We report on a 39-year-old nulligravida who developed rhabdomyolysis after prolonged laparoscopic surgery for cervical cancer and adhesions due to deep infiltrating endometriosis. Minimally invasive surgical procedures offer major advantages in gynecologic cancer surgery, and preventive methods provide effective pressure reduction and play a crucial role in avoiding physical harm after surgical positioning. Nevertheless, a combination of surgical and patient-related risk factors may increase the risk of postsurgical onset of rhabdomyolysis. Immediate referral to a specialist center is necessary to ensure prevention of serious complications. Keywords: Rhabdomyolysis, Gynecologic laparoscopy, Cervical cancer
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- 2018
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62. A retrospective analysis of perioperative complications associated with retropubic tension-free vaginal tape in 960 women
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Janosch Jahn, Christl Reisenauer, Sara Y. Brucker, Birgitt Schoenfisch, Bastian Amend, and Juergen Andress
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Stress incontinence ,medicine.medical_specialty ,Urinary Incontinence, Stress ,Overweight ,Cohort Studies ,Postoperative Complications ,medicine ,Humans ,Aged ,Retrospective Studies ,Suburethral Slings ,Urinary retention ,business.industry ,Tension free vaginal tape ,Obstetrics and Gynecology ,General Medicine ,Perioperative ,Urinary Retention ,medicine.disease ,Surgery ,Treatment Outcome ,Child, Preschool ,Female ,medicine.symptom ,Complication ,business ,Body mass index ,Cohort study - Abstract
Purpose The purpose is to analyse perioperative complications associated with the retropubic tension-free vaginal tape (TVT) procedure and their management. Methods This retrospective, monocentric cohort study included 960 women after retropubic TVT procedure performed by one surgeon from 2011 to 2016. Complications were identified up to 6 weeks after the procedure, divided into specific and general complications and classified based on the Clavien–Dindo (CD) Classification. A visit 6 weeks after the surgical procedure was attended by all patients. Results 77 complications, of which 74 occurred postoperatively and 3 intraoperatively, affecting 72 (7.5%) out of 960 women. Urinary retention and voiding problems were the most common complication. The mean age of women suffering complications was 3.4 years higher in comparison to the mean age of women without complications (p = 0.036). The Body Mass Index (BMI) of the group of women with perioperative complications had an average BMI which was 0.5 kg/m2 lower than the average BMI of the women without complications. 22 (12.8%) out of 172 women with recurrent stress incontinence had postoperative complications, of which 21 were related to the TVT. Conclusion The retropubic TVT is a surgical procedure associated with a low number of perioperative complications, even in the group of elderly and overweight women, as well as in cases of recurrent stress incontinence.
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- 2021
63. Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status
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Matthias W. Beckmann, Lothar Häberle, Christoph Thomssen, Michael P. Lux, Rachel Wuerstlein, Michael Untch, Friedrich Overkamp, Peyman Hadji, Tanja Fehm, Bernhard Volz, Erik Belleville, Alexander Hein, Wolfgang Janni, Hans Tesch, Andreas Schneeweiss, Lena A. Wurmthaler, Christian M. Kurbacher, Johannes Ettl, Carsten Hielscher, Florin-Andrei Taran, Volkmar Müller, Andreas D. Hartkopf, P Wimberger, Sara Y. Brucker, Hans-Christian Kolberg, Diana Lüftner, Diethelm Wallwiener, Peter A. Fasching, Julius Emons, and Markus Wallwiener
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Population ,Breast Neoplasms ,Lapatinib ,HER2/neu ,Trastuzumab ,Internal medicine ,medicine ,Humans ,skin and connective tissue diseases ,education ,neoplasms ,education.field_of_study ,biology ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Metastatic breast cancer ,Clinical trial ,biology.protein ,Female ,business ,medicine.drug - Abstract
Purpose Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.
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- 2021
64. Verteilung des 21-Gen-Rezidiv-Scores bei Patientinnen mit primärem Mammakarzinom in Deutschland
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Markus Hahn, Andreas D. Hartkopf, Sara Y. Brucker, Christina B. Walter, Vincent P. Walter, Markus Wallwiener, Florin-Andrei Taran, Eva-Maria Grischke, and Armin Bauer
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business.industry ,Medicine ,business - Abstract
Zusammenfassung Einleitung Multigen-Assays werden zunehmend als Entscheidungshilfe für eine Chemotherapie beim Mammakarzinom verwendet. Wir stellen hier den 21-Gen-Recurrence-Score (RS) von Patientinnen mit Brustkrebs vor, die routinemäßig in Deutschland untersucht wurden. Patientinnen und Methoden 4695 Patientinnen mit hormonrezeptorpositivem und HER2-negativem Brustkrebs im Frühstadium (pT1–3, pN0–1, M0) wurden einer retrospektiven Analyse unterzogen. Bei diesen Patientinnen wurde in Deutschland zwischen November 2015 und Juli 2018 der Genexpressionstest Oncotype DX zur Ermittlung des Recurrence-Scores durchgeführt. Die Klassifikation der RS-Gruppen erfolgte gemäß der TAILORx Studie (RS: 0–10; 11–25; 26–100). Ergebnisse Von diesen Patientinnen wurden 21 % in die niedrige RS-Gruppe, 63 % in die mittlere RS-Gruppe, und 15 % in die hohe RS-Gruppe eingeteilt. 1772 (81 %) von 2175 Patientinnen im Alter von über 50 Jahren und ohne Lymphknotenbefall wurden entweder in die niedrige oder die mittlere RS-Gruppe eingeteilt. Der Prozentsatz an Patientinnen mit einem niedrigen oder mittleren RS betrug 90 % bei Patientinnen ohne Lymphknotenbefall (1284 von 1432 Patientinnen), 79 % bei Patientinnen mit einem hohen (≥ 20 %) Ki-67-Wert (1829 von 2310 Patientinnen), 86 % bzw. 70 % bei Patientinnen mit G2- bzw. G3-Tumoren (3244 von 3762 Patientinnen bzw. 368 von 522 Patientinnen), 88 % bei Patientinnen mit einem Tumordurchmesser von > 5 cm (140 von 159 Patientinnen) und 82 % bei Patientinnen ohne Lymphknotenbefall, aber mit einem hohen klinischen Risiko (1110 von 1352). Schlussfolgerung Die Verteilung des 21-Gens RS bei deutschen Patientinnen, die in der klinischen Routinepraxis getestet wurden, deutet darauf hin, dass gemäß den Ergebnissen der TAILORx-Studie die Chemotherapie bei den meisten dieser Patientinnen keinen Nutzen hat.
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- 2021
65. Einsatz eines Wendelappens zur Wiederherstellung des Volumens im Achselbereich – ein neuer Behandlungsansatz für die operative Versorgung von sekundären Lymphödemen nach Brustkrebstherapie
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Diethelm Wallwiener, Alexander Florek, Stefan Passin, Susanne Morgenstern, Markus Hahn, Mario Marx, Michael Geßner, and Sara Y. Brucker
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business.industry ,Medicine ,business - Abstract
Zusammenfassung Einleitung Narbige Verengungen und ein Volumendefizit im Bereich der Axilla können zu einem anhaltenden Lymphödem führen und zählen zu den häufigsten Nebenwirkungen nach einer Brustkrebstherapie im Achselbereich. Ziel dieser Arbeit ist die Vorstellung einer Operationstechnik zur Reduzierung von Lymphödemen mithilfe eines Turn-Over Flaps. Material und Methoden Zwischen Oktober 2016 und Mai 2018 wurden 5 Patientinnen mit einem Lymphödem Grad 2 nach Mammakarzinomtherapie mit dieser neuen Methode behandelt. Dabei erfolgte die vollständige Entfernung der kompromittierenden Narbenstränge der Axilla, gefolgt von einer Reaugmentation der Axilla mittels Turn-Over Flap. Danach wurde bei allen Patientinnen eine Brustrekonstruktion mit einer an die thorakodorsalen Gefäße angeschlossenen Fernlappenplastik durchgeführt. Prä- und postoperativ wurden der Umfang beider Arme, die Lebensqualität und die Schmerzen gemessen. Ergebnisse Im Durchschnitt sanken die Schmerzen im ipsilateralen Arm von 6 auf 1 auf der numerischen Schmerzskala, und die Lebensqualität verbesserte sich merklich (2,8 vs. 7,0). Es zeigte sich eine deutliche Verringerung des Lymphödems, vor allem im Oberarm. Komplikationen wie sekundäre Blutungen, Infektionen oder Lappenverlust sind nicht aufgetreten. Schlussfolgerung Eine vollständige Entfernung der nach Brustkrebsbehandlungen entstandenen Vernarbungen im Bereich der Axilla und eine Reaugmentation der Axilla mittels Turn-Over Flap führten zu einer Verringerung des ipsilateralen Lymphödems und zu einer Verbesserung der Schmerzen und der Lebensqualität. Wir deuten dieses Outcome als Ergebnis der physiologischen Ausrichtung der Lymphgefäße und eines lymphknotenhaltigen Transpositionslappens. Die Reaugmentation der Axilla mittels Turn-Over Flap könnte eine wirksame, nicht mikrochirurgische Alternative zur Lymphknotentransplantation darstellen.
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- 2021
66. Retrospective analysis of secondary resection of the cervical stump after subtotal hysterectomy: why and when?
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Christl Reisenauer, Sara Y. Brucker, Bernhard Kraemer, Felix Neis, and Philipp Wagner
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medicine.medical_specialty ,Metrorrhagia ,medicine.medical_treatment ,Subtotal hysterectomy ,Hysterectomy ,Gynaecological disease ,Resection ,medicine ,Retrospective analysis ,Humans ,Cervical stump ,Abdominal hysterectomy ,Secondary resection of the cervical stump ,Retrospective Studies ,business.industry ,Obstetrics and Gynecology ,General Medicine ,medicine.disease ,Resection of the cervix ,Supracervical hysterectomy ,Surgery ,Cervical stump resection ,Dysplasia ,Female ,General Gynecology ,business - Abstract
Purpose The rates of hysterectomy are falling worldwide, and the surgical approach is undergoing a major change. To avoid abdominal hysterectomy, a minimally invasive approach has been implemented. Due to the increasing rates of subtotal hysterectomy, we are faced with the following questions: how often does the cervical stump have to be removed secondarily, and what are the indications? Methods This was a retrospective, single-centre analysis of secondary resection of the cervical stump conducted from 2004 to 2018. Results Secondary resection of the cervical stump was performed in 137 women. Seventy-four percent of the previous subtotal hysterectomy procedures were performed in our hospital, and 26% were performed in an external hospital. During the study period, 5209 subtotal hysterectomy procedures were performed at our hospital. The three main indications for secondary resection of the cervical stump were prolapse (31.4%), spotting (19.0%) and cervical dysplasia (18.2%). Unexpected histological findings (premalignant and malignant) after subtotal hysterectomy resulted in immediate (median time, 1 month) secondary resection of the cervical stump in 11 cases. In four patients, the indication was a secondary malignant gynaecological disease that occurred more than 5 years after subtotal hysterectomy. The median time between subtotal hysterectomy and secondary resection of the cervical stump was 40 months. Secondary resection of the cervical stump was performed vaginally in 75.2% of cases, laparoscopically in 20.4% of cases and abdominally in 4.4% of cases. The overall complication rate was 5%. Conclusion Secondary resection of the cervical stump is a rare surgery with a low complication rate and can be performed via the vaginal or laparoscopic approach in most cases. The most common indications are prolapse, spotting and cervical dysplasia. If a secondary resection of the cervical stump is necessary due to symptoms, 66.6% will be performed within the first 6 years after subtotal hysterectomy.
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- 2021
67. 2022-RA-995-ESGO Independent prognostic significance of substantial lymphovascular space invasion (LVSI) in a consecutive series of primary LVSI-positive endometrial carcinoma (EC)
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Stefan Kommoss, Charlotte Meyer, Marcel Grube, Teresa Praetorius, Sara Y Brucker, Felix Neiss, Bernhard Krämer, Christina Barbara Walter, Friedrich Kommoss, Annette Staebler, Blake Gilks, and Naveena Singh
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- 2022
68. Genome Sequencing and Transcriptome Profiling in Twins Discordant for Mayer-Rokitansky-Küster-Hauser Syndrome
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Schulze-Hentrich, Rebecca Buchert, Elisabeth Schenk, Thomas Hentrich, Nico Weber, Katharina Rall, Marc Sturm, Oliver Kohlbacher, André Koch, Olaf Riess, Sara Y. Brucker, and Julia M.
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MRKH syndrome ,monozygotic discordant twins ,genome sequencing ,transcriptome analysis ,Müllerian ducts - Abstract
To identify potential genetic causes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), we analyzed blood and rudimentary uterine tissue of 5 MRKH discordant monozygotic twin pairs. Assuming that a variant solely identified in the affected twin or affected tissue could cause the phenotype, we identified a mosaic variant in ACTR3B with high allele frequency in the affected tissue, low allele frequency in the blood of the affected twin, and almost absent in blood of the unaffected twin. Focusing on MRKH candidate genes, we detected a pathogenic variant in GREB1L in one twin pair and their unaffected mother showing a reduced phenotypic penetrance. Furthermore, two variants of unknown clinical significance in PAX8 and WNT9B were identified. In addition, we conducted transcriptome analysis of affected tissue and observed perturbations largely similar to those in sporadic cases. These shared transcriptional changes were enriched for terms associated with estrogen and its receptors pointing at a role of estrogen in MRKH pathology. Our genome sequencing approach of blood and uterine tissue of discordant twins is the most extensive study performed on twins discordant for MRKH so far. As no clear pathogenic differences were detected, research to evaluate other regulatory layers are required to better understand the complex etiology of MRKH.
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- 2022
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69. Recurrence Score
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Dominik, Dannehl, Tobias, Engler, Lea L, Volmer, Annette, Staebler, Anna K, Fischer, Martin, Weiss, Markus, Hahn, Christina B, Walter, Eva-Maria, Grischke, Falko, Fend, Florin-Andrei, Taran, Sara Y, Brucker, and Andreas D, Hartkopf
- Abstract
Patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (eBC) with a high risk of relapse often undergo adjuvant chemotherapy. However, only a few patients will gain benefit from chemotherapy. Since classical tumor characteristics (grade, tumor size, lymph node involvement, and Ki67) are of limited value to predict chemotherapy efficacy, multigene expression assays such as the Oncotype DXThe RS result was assessed in patients with HR+/HER2- unilateral eBC with 0-3 pathologic lymph nodes who underwent primary surgical treatment at the Department for Women's Health of Tuebingen University, Germany. Therapy recommendations without knowledge of the RS result were compared to therapy recommendations with awareness of the RS result.In total, 245 patients underwent RS assessment. Without knowledge of the RS result, 92/245 patients (37.6%) would have been advised to receive chemotherapy. After RS assessment, 56/245 patients (22.9%) were advised to undergo chemotherapy. Chemotherapy was waived in 47/92 patients (51.1%) that were initially recommended to receive it. Chemotherapy was added in 11/153 patients (7.2%) that were recommended to not receive it initially.Using the RS result to guide adjuvant treatment decisions in HR+/HER2- breast cancer led to a substantial reduction of chemotherapy. In view of the results achieved in prospective studies, the RS result is among other risk-factors suitable for the individualization of adjuvant systemic therapy.
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- 2022
70. Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
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Felix Ruoff, Nicolas Kersten, Nicole Anderle, Sandra Jerbi, Aaron Stahl, André Koch, Annette Staebler, Andreas Hartkopf, Sara Y. Brucker, Markus Hahn, Katja Schenke-Layland, Christian Schmees, and Markus F. Templin
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Cancer Research ,Oncology ,DigiWest ,breast cancer ,cellular signaling ,PPARγ ,immune cell infiltration ,patient stratification - Abstract
In cancer, the complex interplay between tumor cells and the tumor microenvironment results in the modulation of signaling processes. By assessing the expression of a multitude of proteins and protein variants in cancer tissue, wide-ranging information on signaling pathway activation and the status of the immunological landscape is obtainable and may provide viable information on the treatment response. Archived breast cancer tissues from a cohort of 84 patients (no adjuvant therapy) were analyzed by high-throughput Western blotting, and the expression of 150 proteins covering central cancer pathways and immune cell markers was examined. By assessing CD8α, CD11c, CD16 and CD68 expression, immune cell infiltration was determined and revealed a strong correlation between event-free patient survival and the infiltration of immune cells. The presence of tumor-infiltrating lymphocytes was linked to the pronounced activation of the Jak/Stat signaling pathway and apoptotic processes. The elevated phosphorylation of PPARγ (pS112) in non-immune-infiltrated tumors suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ phosphorylation. Multiplexed immune cell marker assessment and the protein profiling of tumor tissue provide functional signaling data facilitating breast cancer patient stratification.
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- 2022
71. Reassessment of Surgical Procedures for Complex Obstructive Genital Malformations: A Case Series on Different Surgical Approaches
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Alice Hoeller, Sahra Steinmacher, Katharina Schlammerl, Markus Hoopmann, Christl Reisenauer, Valerie Hattermann, Sara Y. Brucker, and Katharina Rall
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obstructive Müllerian duct malformation ,cervical aplasia ,cervical atresia ,hematometra ,uterovaginal anastomosis ,General Medicine - Abstract
The objective of this case series was to describe different uterus-preserving surgical approaches and outcomes in patients with complex obstructive Müllerian duct malformation caused by cervical and/or vaginal anomalies. A retrospective analysis was performed including patients undergoing uterovaginal anastomosis (n = 6) or presenting for follow-up (n = 2) at the Department for Gynecology at the University of Tuebingen between 2017 and 2022. Uterovaginal anastomosis was performed with a one-step combined vaginal and laparoscopic approach (method A), a two-step/primary open abdominal approach with primary vaginal reconstruction followed by abdominal uterovaginal anastomosis after vaginal epithelization (method B) or an attempted one-step approach followed by secondary open abdominal uterovaginal anastomosis due to reobstruction (method A/B). Patients presented at a mean age of 15 years. Two patients were treated by method A, four by method B and two by method A/B. Functional anastomosis was established in seven of eight patients, with normal vaginal length in all patients. Concerning uterovaginal anastomosis, the primary open abdominal approach with or without previous vaginal reconstruction seems to have a higher success rate with fewer procedures and should be implemented as standard surgical therapy for complex obstructive genital malformations including the cervix.
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- 2022
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72. Improved preoperative risk stratification in endometrial carcinoma patients
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Marcel Grube, Casper Reijnen, Peter JF Lucas, Friedrich Kommoss, Felix KF Kommoss, Sara Y Brucker, Christina B Walter, Ernst Oberlechner, Bernhard Krämer, Jürgen Andress, Felix Neis, Annette Staebler, Johanna MA Pijnenborg, Stefan Kommoss, Datamanagement & Biometrics, and Digital Society Institute
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Cancer Research ,Bayesian network ,Oncology ,General Medicine ,Endometrial carcinoma ,Lymph nodes ,Personalized medicine ,Risk stratification - Abstract
Purpose Preoperative risk stratification of newly diagnosed endometrial carcinoma (EC) patients has been hindered by only moderate prediction performance for many years. Recently ENDORISK, a Bayesian network model, showed high predictive performance. It was the aim of this study to validate ENDORISK by applying the model to a population-based case series of EC patients. Methods ENDORISK was applied to a retrospective cohort of women surgically treated for EC from 2003 to 2013. Prediction accuracy for LNM as well as 5-year DSS was investigated. The model’s overall performance was quantified by the Brier score, discriminative performance by area under the curve (AUC). Results A complete dataset was evaluable from 247 patients. 78.1% cases were endometrioid histotype. The majority of patients (n = 156;63.2%) had stage IA disease. Overall, positive lymph nodes were found in 20 (8.1%) patients. Using ENDORISK predicted probabilities, most (n = 156;63.2%) patients have been assigned to low or very low risk group with a false-negative rate of 0.6%. AUC for LNM prediction was 0.851 [95% confidence interval (CI) 0.761–0.941] with a Brier score of 0.06. For 5-year DSS the AUC was 0.698 (95% CI 0.595–0.800) as Brier score has been calculated 0.09. Conclusions We were able to successfully validate ENDORISK for prediction of LNM and 5-year DSS. Next steps will now have to focus on ENDORISK performance in daily clinical practice. In addition, incorporating TCGA-derived molecular subtypes will be of key importance for future extended use. This study may support further promoting of data-based decision-making tools for personalized treatment of EC.
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- 2022
73. Organoide zur Weiterentwicklung der intraoperativen Diagnostik
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N Lipke, Katja Schenke-Layland, Tilman E. Schäffer, Sara Y. Brucker, F Fend, A. Stenzl, H Lensch, N Harland, A Herkommer, Oliver Sawodny, C Tarín Sauer, Wilhelm K. Aicher, and Bastian Amend
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Gynecology ,medicine.medical_specialty ,Geriatric care ,business.industry ,Urology ,medicine ,business - Abstract
Im Rahmen von onkologischen Operationen besteht immer die Abwagung zwischen onkologischer Sicherheit und dem Funktionserhalt. Dies gilt insbesondere bei Operationen im Becken, aufgrund der engen Lagebeziehung zur Muskulatur des Beckenbodens sowie Gefas und Nervenverlaufen. Aktuell dienen zumeist Risikomodelle, praoperative Bildgebung, die Einschatzung des Operateurs sowie der intraoperative Schnellschnitt als Entscheidungsgrundlage. Neue Bildgebungstechniken sowie Standardisierung im Schnellschnitt haben diese in den letzten Jahren deutlich verbessert. Es verbleiben jedoch weiterhin Einschrankungen durch zeitliche Verzogerung sowie erschwerte korrekte anatomische Zuordnung der zu untersuchenden Praparate. Alternative intraoperative Verfahren konnten diese Grenzen in der Zukunft uberwinden. Patientenabgeleitete Organoide haben sich in den letzten Jahren zu einem wichtigen neuen Forschungsvehikel entwickelt. Sie basieren auf Tumorstammzellen, die unter speziellen Kulturbedingungen dreidimensionale Replikate des Ursprungsgewebes formen. Damit sind sie optimal geeignet zur Testung von individuellen Systemtherapien aber auch als Validierungstechnik fur neue diagnostische Verfahren. Das durch die Deutsche Forschungsgemeinschaft geforderte Graduiertenkolleg 2543/I analysiert in einem interdisziplinaren Team das Potenzial neuer diagnostischer Methoden im Hinblick auf die intraoperative real-time Diagnostik in Erganzung zu konventionellen Schnellschnittdiagnostik
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- 2021
74. The SOX2 Status of Disseminated Tumor Cells in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy
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Sara Y. Brucker, Hans Neubauer, Diethelm Wallwiener, Tanja Fehm, Annette Staebler, Natalia Krawczyk, Maggie Banys-Paluchowski, Christoph Meisner, Kathrin Janowski, and Andreas D. Hartkopf
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Tumor cells ,Cohort Studies ,Breast cancer ,Bone marrow aspirate ,stomatognathic system ,SOX2 ,Internal medicine ,Humans ,Medicine ,Chemotherapy ,biology ,business.industry ,SOXB1 Transcription Factors ,fungi ,General Medicine ,Middle Aged ,medicine.disease ,Minimal residual disease ,Primary tumor ,Treatment Outcome ,Chemotherapy, Adjuvant ,embryonic structures ,biology.protein ,Female ,sense organs ,biological phenomena, cell phenomena, and immunity ,Antibody ,business - Abstract
Background/aim Detection of disseminated tumor cells (DTCs) after systemic treatment predicts poor prognosis in breast cancer patients. The aim of our study was to assess the expression of stem-cell marker SOX2 on DTCs and in the primary tumor of patients treated with neoadjuvant chemotherapy (NAT). Materials and methods In 170 DTC-positive patients after NAT an additional slide of bone marrow aspirate was stained by double immunofluorescence to detect SOX2-positive DTCs. The SOX2 status of the primary tumor was assessed using the same antibody. Results The SOX2-status of DTCs was determined in 62 patients and 20 of those (32%) had SOX2 positive DTCs. The SOX2 status of DTCs was not associated with any of the clinicopathological factors. A total of 36% of the patients with a SOX2-negative tumor showed SOX2-positive persistent DTCs. Conclusion SOX2-positive DTCs can be detected in breast cancer patients after NAT, even in patients with SOX2-negative primary tumors. This suggests that these populations may have evolved independently of each other.
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- 2021
75. Behandlung von Patientinnen mit frühem Mammakarzinom: Evidenz, Kontroversen, Konsens – Meinungsbild deutscher Expert*innen zur 17. Internationalen St.-Gallen-Konsensuskonferenz
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Sibylle Loibl, Renate Haidinger, Sara Y. Brucker, Nadia Harbeck, Jens Huober, Cornelia Kolberg-Liedtke, Christoph Thomssen, Thorsten Kühn, Carsten Denkert, Christian Jackisch, Peter A. Fasching, Wolfgang Janni, Andreas Schneeweiss, Volkmar Müller, David Krug, Diana Lüftner, Michael Untch, Wilfried Budach, and Marc Thill
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Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,030212 general & internal medicine ,business ,Early breast cancer - Abstract
ZusammenfassungDie diesjährige 17. St.-Gallen(SG)-Konsensus-Konferenz zur Behandlung von Patientinnen mit frühem Mammakarzinom (SG-BCC) stand unter dem Motto „Customizing local and systemic therapies for women with early breast cancer“ und fokussierte auf die Herausforderung, die Behandlung des frühen Mammakarzinoms zielgerichteter auf die individuelle Krankheitssituation zu adaptieren. Wie schon in den vergangenen Jahren hat auch dieses Jahr eine deutsche Arbeitsgruppe führender Brustkrebsexpert*innen die Ergebnisse der internationalen SG-BCC 2021 vor dem Hintergrund der deutschen Therapieempfehlungen für den Klinikalltag in Deutschland diskutiert. Der Vergleich der SG-Empfehlungen mit den erst kürzlich aktualisierten Therapieempfehlungen der Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) sowie der S3-Leitlinie ist hilfreich, da sich das SG-BCC-Panel aus Experten unterschiedlicher Länder zusammensetzt, weshalb länderspezifische Besonderheiten in die SG-Empfehlungen einfließen können. Die deutschen Therapieempfehlungen der AGO sowie der S3-Leitlinie basieren auf der aktuellen Evidenz. Gleichwohl muss jede Therapieentscheidung immer einer Nutzen-Risiko-Abwägung für die individuelle Situation unterzogen und mit der Patientin besprochen werden.
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- 2021
76. Uterustransplantation durch Lebendspende bei absoluter uteriner Infertilität
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Andrina Kölle, Sara Y. Brucker, Sahra Steinmacher, Silvio Nadalin, and Katharina Rall
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Gynecology ,Transplantation ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Uterus ,medicine ,General Medicine ,business - Published
- 2021
77. Adhesion prevention after endometriosis surgery — results of a randomized, controlled clinical trial with second-look laparoscopy
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S Hoffmann, Jürgen Andress, Sara Y. Brucker, Alice Höller, Stefan Kommoss, Bernhard K. Krämer, and Felix Neis
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Barrier gel ,medicine.medical_specialty ,Ileus ,medicine.medical_treatment ,Endometriosis ,Adhesion (medicine) ,Tissue Adhesions ,Controlled Clinical Trials ,Clinical study ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Saline ,030219 obstetrics & reproductive medicine ,business.industry ,Adhesion barrier ,Vascular surgery ,medicine.disease ,Surgery ,Clinical trial ,Cardiothoracic surgery ,Deep infiltrating endometriosis ,Second look ,030220 oncology & carcinogenesis ,Adhesion prophylaxis ,Female ,Laparoscopy ,4DryField® PH ,business ,Abdominal surgery - Abstract
Purpose Adhesion formation after endometriosis surgery is a severe problem affecting up to 90% of patients. Possible complications include chronic pain, ileus, and secondary infertility. Therefore, effective adhesion prophylaxis is desirable, for which the adhesion barrier 4DryField® PH is evaluated in the present clinical study. It is a starch-based powder that forms a gel after irrigation with saline solution and thus separates surgical sites as physical barrier for adhesion prevention. Methods Fifty patients with extensive and deep infiltrating endometriosis were included in this prospective, randomized, controlled clinical trial with two-staged laparoscopic approach. The patients were randomized into two groups, one receiving 4DryField® PH and the other irrigation with saline solution for adhesion prevention. Adhesion formation was directly scored during second-look interventions considering incidence, extent, and severity. Adhesion prevention treatment in the second surgery was performed corresponding to the first intervention to evaluate the long-term outcome in the later course. Results Both groups were comparable with respect to relevant patient parameters. Severity and extent of adhesions were significantly reduced by 85% in the 4DryField® PH group compared to the control group (mean total adhesion score 2.2 vs. 14.2; p = 0.004). Incidence of adhesion formation based on the number of affected sites was significantly reduced by 53% in the intervention vs. control group (mean 1.1 vs. 2.3 sites; p = 0.004). Follow-up of secondary endpoints is not yet completed; results will become available at a later stage. Conclusion Adhesion formation could be reduced significantly by 85% by application of the adhesion barrier 4DryField® PH. Trial registration Trial registration main ID: DRKS00014720, secondary ID: U1111-1213-4142; date of registration 09th May 2018.
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- 2021
78. Interest in Integrative Medicine Among Postmenopausal Hormone Receptor–Positive Breast Cancer Patients in the EvAluate-TM Study
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Carolin C. Hack MD, Peter A. Fasching MD, Tanja Fehm MD, Johann de Waal MD, Mahdi Rezai MD, Bernd Baier MD, Gerold Baake MD, Hans-Christian Kolberg MD, Martin Guggenberger MD, Mathias Warm MD, Nadia Harbeck MD, Rachel Wuerstlein MD, Jörg-Uwe Deuker MD, Peter Dall MD, Barbara Richter MD, Grischa Wachsmann MD, Cosima Brucker MD, Jan W. Siebers MD, Nikos Fersis MD, Thomas Kuhn MD, Christopher Wolf MD, Hans-Walter Vollert MD, Georg-Peter Breitbach MD, Wolfgang Janni MD, Robert Landthaler MD, Andreas Kohls MD, Daniela Rezek MD, Thomas Noesslet MD, Gunnar Fischer MD, Stefan Henschen MD, Thomas Praetz MD, Volker Heyl MD, Thorsten Kühn MD, Thomas Krauss MD, Christoph Thomssen MD, Andre Hohn MD, Hans Tesch MD, Christoph Mundhenke MD, Alexander Hein MD, Claudia Rauh MD, Christian M. Bayer MD, Adib Jacob, Katja Schmidt PhD, Erik Belleville PhD, Peyman Hadji MD, Sara Y. Brucker MD, Diethelm Wallwiener MD, Sherko Kümmel MD, Matthias W. Beckmann MD, and Daniela Paepke MD
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background . Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods . The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor–positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Results . Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. Conclusions . This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.
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- 2017
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79. Information ranks highest: Expectations of female adolescents with a rare genital malformation towards health care services.
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Elisabeth Simoes, Alexander N Sokolov, Andrea Kronenthaler, Hanna Hiltner, Norbert Schaeffeler, Katharina Rall, Esther Ueding, Monika A Rieger, Anke Wagner, Leonie S Poesch, Marie-Christin Baur, Judith Kittel, and Sara Y Brucker
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Medicine ,Science - Abstract
Access to highly specialized health care services and support to meet the patient's specific needs is critical for health outcome, especially during age-related transitions within the health care system such as with adolescents entering adult medicine. Being affected by an orphan disease complicates the situation in several important respects. Long distances to dedicated institutions and scarcity of knowledge, even among medical doctors, may present major obstacles for proper access to health care services and health chances. This study is part of the BMBF funded TransCareO project examining in a mixed-method design health care provisional deficits, preferences, and barriers in health care access as perceived by female adolescents affected by the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), a rare (orphan) genital malformation.Prior to a communicative validation workshop, critical elements of MRKHS related care and support (items) were identified in interviews with MRKHS patients. During the subsequent workshop, 87 persons involved in health care and support for MRKHS were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1, strongly disagree) as to 1) the elements' potential importance (i.e., health care expected to be "best practice", or priority) and 2) the presently experienced care. A gap score between the two was computed highlighting fields of action. Items were arranged into ten separate questionnaires representing domains of care and support (e.g., online-portal, patient participation). Within each domain, several items addressed various aspects of "information" and "access". Here, we present the outcome of items' evaluation by patients (attended, NPAT = 35; respondents, NRESP = 19).Highest priority scores occurred for domains "Online-Portal", "Patient participation", and "Tailored informational offers", characterizing them as extremely important for the perception as best practice. Highest gap scores yielded domains "Tailored informational offers", reflecting perceived lack of disease-related information for affected persons, medical experts, and health insurance companies, "Online-Portal" (with limited information available on specialist clinics and specialized doctors), and regarding insufficient support offers (e.g., in school and occupational settings). Conversely, lowest gap scores were found with group offers for MRKHS patients ("Transition programs") and MRKHS self-help days ("Patient participation"), suggesting satisfaction or good solutions in place.The importance assigned to disease-related information indicates that informational deficits are perceived by patients as barriers, hindering proper access to health care, especially in an orphan disease. Access to health-related information plays a role for all persons seeking help and care. However, the overwhelmingly high scores attributed to these elements in the context of an orphan disease reveal that here improved information policies are crucial, demanding for institutionalized solutions supported by the health care system.The disparity between experience of care and attribution as best practice detected describes areas of action in all domains involved, highlighting information related fields. New concepts and structures for health care in orphan diseases could draw upon these patient-oriented results a) regarding orphan-disease specific elements demanding institutionalized reimbursement, b) essential elements for center care and corresponding networks, and c) elements reflecting patients´ participation in the conception of centers for rare diseases.
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- 2017
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80. Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1).
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Philipp Harter, Jan Hauke, Florian Heitz, Alexander Reuss, Stefan Kommoss, Frederik Marmé, André Heimbach, Katharina Prieske, Lisa Richters, Alexander Burges, Guido Neidhardt, Nikolaus de Gregorio, Ahmed El-Balat, Felix Hilpert, Werner Meier, Rainer Kimmig, Karin Kast, Jalid Sehouli, Klaus Baumann, Christian Jackisch, Tjoung-Won Park-Simon, Lars Hanker, Sandra Kröber, Jacobus Pfisterer, Heidrun Gevensleben, Andreas Schnelzer, Dimo Dietrich, Tanja Neunhöffer, Mathias Krockenberger, Sara Y Brucker, Peter Nürnberg, Holger Thiele, Janine Altmüller, Josefin Lamla, Gabriele Elser, Andreas du Bois, Eric Hahnen, and Rita Schmutzler
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Medicine ,Science - Abstract
Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16-93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2 (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes) in patients
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- 2017
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81. Genome Sequencing and Transcriptome Profiling in Twins Discordant for Mayer-Rokitansky-Küster-Hauser Syndrome
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Rebecca Buchert, Elisabeth Schenk, Thomas Hentrich, Nico Weber, Katharina Rall, Marc Sturm, Oliver Kohlbacher, André Koch, Olaf Rieß, Sara Y. Brucker, and Julia M. Schulze-Hentrich
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ObjectiveMayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a rare congenital disease manifesting with aplasia or severe hypoplasia of uterine structures. Even though extensive studies have been performed, for the majority of cases the etiology remains unclear. In this study, we sought to identify genetic causes in discordant monozygotic (MZ) twins using genome sequencing of blood of both twins as well as uterine tissue of the affected twin. In addition, we profiled the endometrial transcriptome of affected twins to compare perturbations with those of sporadic MRKH cases.ResultsFirst, analyzing the data under the assumption that a variant solely identified in the affected twin or affected tissue could cause the phenotype, we identified a mosaic variant in ACTR3B with a high allele frequency in affected tissue, a low allele frequency in blood of the affected twin and almost absent in the blood of the unaffected twin. Since ACTR3B has not been reported for genitourinary anomalies before, clinical relevance of the variant needs to be clarified.Second, examining the data for candidate genes previously implied in MRKH, we detected a pathogenic variant in GREB1L in one twin pair and their unaffected mother showing a reduced phenotypic penetrance. Furthermore, two variants of unknown clinical significance in PAX8 and WNT9B were identified. Analysis for copy number and structural variants revealed no discordant variants in the twins or variants in candidate genes or regions.Third, we conducted transcriptome analysis of affected tissue and observed widespread perturbations largely similar to those in sporadic MRKH cases. These shared transcriptional changes were enriched for terms associated with estrogen and its receptors pointing at a key role of estrogen in MRKH pathology.ConclusionOur study on genome sequencing of blood and uterine tissue of discordant twins is the most extensive study performed on twins discordant for MRKH so far. Nevertheless, no clear pathogenic differences in the twins or between blood and tissue samples were detected. This points towards a more complex etiology of MRKH less dependent on genetic differences and more determined by epigenetic changes or environmental factors. Our transcriptome data showed a clear overlap with gene expression data of sporadic MRKH cases, indicating that the etiology for MRKH in discordant twins and sporadic cases is largely similar.
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- 2022
82. Return of individual genomic research results within the PRAEGNANT multicenter registry study
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Hanna Huebner, Matthias Ruebner, Christian Kurbacher, Peyman Hadji, Andreas D. Hartkopf, Michael P. Lux, Jens Huober, Sabrina Uhrig, Florin-Andrei Taran, Friedrich Overkamp, Hans Tesch, Lothar Häberle, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Matthias W. Beckmann, Alexander Hein, Erik Belleville, Michael Untch, Wolfgang Janni, Tanja N. Fehm, Hans-Christian Kolberg, Diethelm Wallwiener, Sara Y. Brucker, Andreas Schneeweiss, Johannes Ettl, Peter A. Fasching, and Laura L. Michel
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Cancer Research ,Oncology - Abstract
Purpose The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient’s quality of life) using a questionnaire. Methods 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient’s quality of life. Results 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients’ health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. Conclusion This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.
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- 2022
83. Intraoperative Ultrasound-Guided Excision of Non-Palpable and Palpable Breast Cancer: Systematic Review and Meta-Analysis
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Maggie Banys-Paluchowski, Isabel T. Rubio, Güldeniz Karadeniz Cakmak, Antonio Esgueva, Natalia Krawczyk, Peter Paluchowski, Ines Gruber, Mario Marx, Sara Y Brucker, Nana Bündgen, Thorsten Kühn, Achim Rody, Lars Hanker, and Markus Hahn
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Humans ,Margins of Excision ,Radiology, Nuclear Medicine and imaging ,Breast Neoplasms ,Female ,Ultrasonography, Mammary ,Neoplasm Recurrence, Local ,Mastectomy, Segmental ,Ultrasonography, Interventional - Abstract
Wire-guided localization (WGL) is the most frequently used localization technique in non-palpable breast cancer (BC). However, low negative margin rates, patient discomfort, and the possibility of wire dislocation have been discussed as potential disadvantages, and re-operation due to positive margins may increase relapse risk. Intraoperative ultrasound (IOUS)-guided excision allows direct visualization of the lesion and the resection volume and reduces positive margins in palpable and non-palpable tumors. We performed a systematic review on IOUS in breast cancer and 2 meta-analyses of randomized clinical trials (RCTs). In non-palpable BC, 3 RCTs have shown higher negative margin rates in the IOUS arm compared to WGL. Meta-analysis confirmed a significant difference between IOUS and WGL in terms of positive margins favoring IOUS (risk ratio 4.34, p0.0001, I2 = 0%). 41 cohort studies including 3291 patients were identified, of which most reported higher negative margin and lower re-operation rates if IOUS was used. In palpable BC, IOUS was compared to palpation-guided excision in 3 RCTs. Meta-analysis showed significantly higher rates of positive margins in the palpation arm (risk ratio 2.84, p = 0.0047, I2 = 0%). In 13 cohort studies including 942 patients with palpable BC, negative margin rates were higher if IOUS was used, and tissue volumes were higher in palpation-guided cohorts in most studies. IOUS is a safe noninvasive technique for the localization of sonographically visible tumors that significantly improves margin rates in palpable and non-palpable BC. Surgeons should be encouraged to acquire ultrasound skills and participate in breast ultrasound training.Drahtlokalisation stellt die am häufigsten verwendete Lokalisationsmethode bei nicht palpablen Mammakarzinomen dar. Zu potenziellen Nachteilen der Technik gehören eine niedrige Rate an R0-Resektionen, die Invasivität und das Risiko der Drahtdislokation. Des Weiteren ist die Notwendigkeit einer Re-Operation mit einem erhöhten Rezidivrisiko assoziiert. Intraoperative Sonografie (IOUS) erlaubt eine direkte Visualisierung der Läsion und des Resektionsvolumens und reduziert die Rate an positiven Rändern bei palpablen und nicht palpablen Tumoren. Wir führten ein systematisches Review der Studien zur IOUS durch. Die randomisierten Studien wurden in 2 Metaanalysen ausgewertet. In nicht palpablen Mammakarzinomen zeigten3 randomisierte Studien höhere R0-Resektionsraten im IOUS-Arm, verglichen mit Drahtlokalisation. Der signifikante Unterschied konnte in der Metaanalyse bestätigt werden (Risk Ratio 4,34, p0,0001, I2 = 0%). Die meisten der 41 Kohortenstudien mit 3291 Patientinnen zeigten höhere R0-Resektionsraten und niedrigere Nachresektionsraten bei Verwendung von IOUS. Eine Metaanalyse von 3 randomisierten Studien bei palpablem Mammakarzinom zeigte signifikant höhere Raten an positiven Rändern im Palpations-Arm (Risk Ratio 2,84, p = 0,0047, I2 = 0%). In 13 Kohortenstudien mit 942 Patientinnen mit palpablem Mammakarzinom, waren die R0-Resektionsraten meist höher und die Gewebsvolumina niedriger, bei Verwendung von IOUS. IOUS ist eine sichere nicht invasive Technik zur Lokalisation von sonografisch sichtbaren Tumoren und verbessert R0-Resektionsraten bei palpablem und nicht palpablem Mammakarzinom. Sonografische Weiterbildung für Brustoperateure erscheint empfehlenswert.
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- 2022
84. Protein profiling of breast carcinomas reveals expression of immune-suppressive factors and signatures relevant to patient outcome
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Felix Ruoff, Nicolas Kersten, Nicole Anderle, Sandra Jerbi, Aaron Stahl, André Koch, Anette Staebler, Andreas Hartkopf, Sara Y. Brucker, Markus Hahn, Katja Schenke-Layland, Christian Schmees, and Markus F. Templin
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BackgroundIn cancerous tissue, a complex interplay of tumour cells with different cell types from the tumour microenvironment is causing modulations in signalling processes. By directly assessing expression of a multitude of proteins and protein variants, extensive information on signalling pathways, their activation status and the effect of the immunological landscape can be obtained providing viable information for treatment response.MethodsProtein extracted from archived breast cancer tissue from patients without adjuvant therapy was subjected to high-throughput Western blotting using the DigiWest technology. Expression of 150 proteins and protein variants covering cell cycle control, apoptosis, Jak/Stat, MAPK-, Pi3K/Akt-, Wnt-, and, autophagic signalling as well as general tumour markers was monitored in a cohort of 84 patient samples. The degree of immune cell infiltration was investigated and set against treatment outcome by integrating patient specific follow-up data.ResultsCharacterization of the tumour microenvironment by monitoring CD8α, CD11c, CD16 and CD68 expression revealed a strong correlation of event-free patient survival with immune cell infiltration. Furthermore, the presence of tumour infiltrating lymphocytes was linked to a pronounced activation of the Jak/Stat signalling pathway and apoptotic processes. Elevated phosphorylation of peroxisome proliferator-activated receptor gamma (PPARγ, pS112) in non-immune infiltrated tumour tissue suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ activation.ConclusionMultiplexed immune cell marker assessment and protein profiling of tumour tissue provides functional signalling data facilitating breast cancer patient stratification.
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- 2022
85. Breast cancer risk factors and survival by tumor subtype
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Päivi Auvinen, Hoda Anton-Culver, Stig E. Bojesen, Gad Rennert, Christos Petridis, Taru A. Muranen, Lukas Schwentner, Jenny Chang-Claude, Chen-Yang Shen, Melissa A. Troester, Sara Y. Brucker, Miriam Dwek, Jingmei Li, Nadia Obi, Montserrat Garcia-Closas, Soo Hwang Teo, Pascal Guénel, Hidemi Ito, Sabine Behrens, Rulla M. Tamimi, Melissa C. Southey, Michelle D. Holmes, Christopher A. Haiman, Henrik Flyger, Roger L. Milne, Per Hall, Jyh-Cherng Yu, Thomas U. Ahearn, William G. Newman, D. Gareth Evans, Dong-Young Noh, Qin Wang, Robert Winqvist, Tjoung-Won Park-Simon, Angela Cox, Dimitrios Mavroudis, Federico Canzian, Celine M. Vachon, Annelie Augustinsson, Shivaani Mariapun, Keitaro Matsuo, Mia M. Gaudet, Anna Jakubowska, Loic Le Marchand, Rob A. E. M. Tollenaar, Paul D.P. Pharoah, Mikael Hartman, Jane Heyworth, Alison M. Dunning, Daniele Campa, Keun-Young Yoo, Anna Morra, Sileny Han, Anna H. Wu, David J. Hunter, Laura E. Beane Freeman, Mehdi Manoochehri, Volker Arndt, Elinor J. Sawyer, Peter A. Fasching, Alicja Wolk, Xiao-Ou Shu, José A. García-Sáenz, Hermann Brenner, Børge G. Nordestgaard, Pooja Middha Kapoor, Diether Lambrechts, Kamila Czene, Marjanka K. Schmidt, Nadege Presneau, Stephen J. Chanock, Mervi Grip, Ignacio Briceño, Stella Koutros, Nicola J. Camp, Kathleen M. Egan, Wei Zheng, Reiner Hoppe, Simon S. Cross, James V. Lacey, Manjeet K. Bolla, Cari M. Kitahara, Annika Lindblom, Carl Blomqvist, William J. Tapper, Diana Torres, Jan Lubinski, Milena Jakimovska, Vessela N. Kristensen, Jose E. Castelao, Graham G. Giles, Andrew F. Olshan, John L. Hopper, A. Heather Eliassen, Valerie Rhenius, Christopher G. Scott, Agnes Jager, Thilo Dörk, Justin A. Williams, Ian Tomlinson, Emmanouil Saloustros, Ji Yeob Choi, Dijana Plaseska-Karanfilska, Thérèse Truong, Audrey Y. Jung, Daehee Kang, Argyrios Ziogas, Peter Kraft, Arto Mannermaa, Rudolf Kaaks, Heiko Becher, Wolfgang Janni, Niclas Håkansson, Steven N. Hart, Xiaohong R. Yang, Håkan Olsson, Fergus J. Couch, Renske Keeman, Ute Hamann, Atocha Romero, Daniel O. Stram, Andreas Schneeweiss, Susan M. Gapstur, Michael Lush, Diana Eccles, Sara Margolin, Hedy S. Rennert, Muhammad Usman Rashid, Mitul Shah, Matthias W. Beckmann, Sophia S. Wang, Douglas F. Easton, Manuela Gago-Dominguez, Christine L. Clarke, and Medical Oncology
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Epidemiology ,Estrogen receptor ,Breast Neoplasms ,Article ,03 medical and health sciences ,Aged ,Cause of Death ,Female ,Humans ,Middle Aged ,Neoplasm Invasiveness ,Neoplasm Staging ,Prospective Studies ,Risk Factors ,Survival Analysis ,Life Style ,0302 clinical medicine ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,business.industry ,Proportional hazards model ,Cancer ,medicine.disease ,Confidence interval ,3. Good health ,Tumor Subtype ,030104 developmental biology ,Clinical research ,030220 oncology & carcinogenesis ,business ,Body mass index - Abstract
Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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- 2021
86. Abstract PS17-42: A fast and effective 3D preclinical assay system comprised of patient derived breast cancer microtumors combined with DigiWest protein signaling pathway analyses for therapeutic response prediction (Project PRIMO)
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Sara Y. Brucker, Felix Ruoff, Markus F. Templin, Nicole Anderle, André Koch, Simge G Yuez, Michael Pawlak, Christian Schmees, and Andreas D. Hartkopf
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Cancer Research ,Tumor microenvironment ,business.industry ,Cancer ,medicine.disease ,Primary tumor ,Efficacy ,Breast cancer ,Immune system ,Oncology ,medicine ,Cancer research ,Personalized medicine ,Viability assay ,business - Abstract
In the era of personalized medicine, the ability of pre-selecting individualized therapeutic options and pre-defining their suitability in advance of clinical treatment might facilitate decision making in breast cancer treatment and hence, improve patient outcome. In order to preclinically validate anti-cancer drug efficacy, it is crucial to design a model system that reveals the influence of cellular interactions of the tumor microenvironment and cellular heterogeneity on drug response. Within the PRIMO (Personalized Medicine for tailored cancer therapies) project, such a 3D preclinical model system comprised of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) isolated from fresh primary breast cancer tissue using limited digestion and subsequent culture in defined media in the absence of serum is established. Herein, the heterogeneous cellular composition of isolated PDM is analyzed by FFPE immunohistochemistry and compared to corresponding primary tumor tissue. The composition of autologous TILs influencing individual treatment responses is characterized by multi-color flow cytometry detecting different cell populations, such as tumor-specific CD8+ or regulatory CD4+ T-cells. By using the DigiWest technology, a proprietary high throughput immune assay screening tool, in-depth protein profiling of up to 200 analytes from low amounts of PDM material is performed. The generated protein profiles of PDM are compared to their corresponding primary tumor tissue as well as the pathological receptor grading. Furthermore, differences in activation of key signal transduction pathways are detected and related to treatment responses to small molecules, chemotherapeutics as well as immunotherapeutic agents within PDM and PDM-TIL co-cultures assessed by a functional viability assay in a microplate format. To expand this preclinical model system, we established PDM-co-cultures adding further immune cell types including natural killer (NK) cells or dendritic cells (DC). In summary, immunohistochemical analyses combined with protein profiling of breast cancer PDM enables drug-mode-of-action analyses, biomarker identification together with personalized therapeutic sensitivity prediction. The platform presented here expands the preclinical repertoire of relevant test systems for efficacy testing of drugs and investigational compounds, pre-identified by protein pathways as well as genetic profiling in personalized medicine of breast cancer. Citation Format: Nicole Anderle, Felix Ruoff, Simge Yuez, André Koch, Andreas Hartkopf, Sara Brucker, Michael Pawlak, Markus Templin, Christian Schmees. A fast and effective 3D preclinical assay system comprised of patient derived breast cancer microtumors combined with DigiWest protein signaling pathway analyses for therapeutic response prediction (Project PRIMO) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-42.
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- 2021
87. Abstract PS10-31: Ribecca - a phase 3b, multi-center, open label study for women with estrogen receptor positive, locally advanced or metastatic breast cancer treated with ribociclib (lee011) in combination with letrozole: Final results
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Wolfgang Janni, Hans Tesch, Mattea Reinisch, J Schubert, Christian M. Kurbacher, Andreas D. Hartkopf, Martin Schuler, Tanja Fehm, Arndt Nusch, Diana Lüftner, Petra Krabisch, Thomas Decker, Roswitha Fuchs, Sara Y. Brucker, Peter A. Fasching, Andreas Schneeweiss, Claudia Voges, Bernhard Heinrich, and Sherko Kuemmel
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Cancer Research ,medicine.medical_specialty ,business.industry ,Letrozole ,medicine.medical_treatment ,Cancer ,medicine.disease ,Metastatic breast cancer ,Gastroenterology ,Radiation therapy ,Breast cancer ,Oncology ,Internal medicine ,Clinical endpoint ,medicine ,Population study ,Progression-free survival ,business ,medicine.drug - Abstract
Introduction: RIBECCA is a national, multi-center, open-label, single-arm phase IIIb trial assessing the efficacy and safety of ribociclib in combination with letrozole in a patient population similar to the populations of MONALEESA-2, -3 and -7, including premenopausal and postmenopausal patients without pretreatment as well as patients with up to 3 previous treatment lines for advanced disease. Here we present the final analysis for the primary endpoint. Methods:The study enrolled women or men with metastatic or locally advanced breast cancer irrespective of their menopausal status, who were not amenable to curative treatment by surgery or radiotherapy. Histological or cytological confirmation of HR+, HER2- breast cancer was required. 502 patients were enrolled in two Cohorts. Cohort A (n=319): postmenopausal women and men without pretreatment for advanced disease; Cohort B (n=183): premenopausal women without pretreatment for advanced disease and pre- or postmenopausal women and men with ≤ 1 line of chemotherapy and/or ≤ 2 lines of endocrine therapy in the advanced situation. The primary endpoint was to assess the clinical benefit rate (CBR, defined as CR, PR or SD, or NCRNPD) at 24 weeks for the overall study population. Secondary endpoints included: progression free survival (PFS), overall survival (OS), safety, and changes in quality of life as assessed by EORTC QLQ-C30 and -BR23 questionnaires. Results: The study ended 84 weeks after the enrollment of the last patient. The median observation time was 10.6 months (0.1-38 months). Baseline characteristics: of 502 pts, 5 were male, 497 were female(46 pre-or perimenopausal, 451 postmenopausal); median age: 64 yrs; ECOG 0-1: 96.8%; 71.1 % of pts had bone metastases (40.8% bone only), 30.6% liver, 27.5% lung and 30.1% other metastases. 97.3% had at least 1 metastatic site: 48.7% had 1, 35.1% had 2, 12.9% had 3 and 1.6% had 4 metastatic sites, respectively. 78.9% received at least one prior antineoplastic therapy: 4.9% received neoadjuvant, 56.8% adjuvant and 37.8% palliative treatment as last antineoplastic therapy before study start. The most common treatment emergent AEs (all grades) were neutropenia and/or neutrophil count decreased (60.6%), nausea (42%), fatigue (39.2%), alopecia (35.1%), leukopenia or WBC decreased (30.7%), nasopharyngitis (28.5%), diarrhea (25.3%), ALT increased (22.9%) and AST increased (20.7%). The CBR at week 24 for the overall study population was 69.2%. Median PFS was 16.5 [95%CI 13.7; 19.3] months in the overall study population, 21.8 [15.4; 25.3] months and 9.3 [8.1; 16.3] months in Cohort A and B, respectively. At 72 weeks, the Kaplan-Meier estimate for OS was 86.8% [83.3; 89.6]. Because of the low number of events during the study period, median OS could not be determined. Conclusion: The results of the final analysis confirmed clinical benefit of ribociclib and letrozole in this patient population. No new safety signals emerged. Citation Format: Mattea Reinisch, Arndt Nusch, Thomas Decker, Andreas Hartkopf, Bernhard J Heinrich, Christian M Kurbacher, Roswitha Fuchs, Hans Tesch, Petra Krabisch, Sara Y Brucker, Tanja Fehm, Wolfgang Janni, Sherko Kuemmel, Diana Lüftner, Andreas Schneeweiss, Martin Schuler, Claudia Voges, Joerg Schubert, Peter A Fasching. Ribecca - a phase 3b, multi-center, open label study for women with estrogen receptor positive, locally advanced or metastatic breast cancer treated with ribociclib (lee011) in combination with letrozole: Final results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-31.
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- 2021
88. Fertility preserving management of early endometrial cancer in a patient cohort at the department of women’s health at the university of Tuebingen
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Christina B. Walter, Jürgen Andress, Andreas D. Hartkopf, Sahra Steinmacher, Stefan Kommoss, Bernhard K. Krämer, J Pasternak, Birgitt Schönfisch, and Sara Y. Brucker
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Adult ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,medicine.drug_class ,medicine.medical_treatment ,Endometrium ,Conservative Treatment ,Atypical hyperplasia ,Fertility sparing treatment ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Germany ,Medicine ,Humans ,Low-grade endometrial cancer ,Complex atypical hyperplasia ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Hysterectomy ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Endometrial cancer ,Obstetrics and Gynecology ,Fertility Preservation ,General Medicine ,Gynecologic Oncology ,medicine.disease ,Curettage ,Endometrial Neoplasms ,Progestin agents ,medicine.anatomical_structure ,Fertility ,Treatment Outcome ,Hysteroscopy ,030220 oncology & carcinogenesis ,Cohort ,Endometrial Hyperplasia ,Female ,Progestins ,business ,Progestin ,Organ Sparing Treatments - Abstract
Purpose To investigate the oncologic and reproductive outcome of a conservative treatment with progestin agents in early-stage grade 1 endometrial cancer (G1EC), grade 2 endometrial cancer (G2EC) or complex atypical hyperplasia (CAH) in young premenopausal women. Methods Women treated for early-stage endometrial cancer or atypical hyperplasia of the endometrium with a conservative therapy between 2006 and 2018 were enrolled in this retrospective analysis. Progestin agents were orally administered on a daily basis for 3 months for at least one cycle. Endometrial tissue was obtained by hysteroscopy and Dilatation & Curettage (D&C) being performed before and after end of treatment. Therapeutic response was assessed by pathological examination. Results A total of 14 patients were included. After treatment with progestin agents, 11 of these patients initially showed a complete or partial response. Three patients with early-stage endometrial cancer did not respond. Of the three patients with initially diagnosed atypical hyperplasia, none showed any remaining disease later. Of the eight patients with initially diagnosed endometrial cancer, who had responded to first treatment, three patients were re-diagnosed with endometrial cancer later. One patient with initial endometrial cancer became pregnant but aborted in the 10th week. Conclusion Due to its good efficacy, progestin agents offer a feasible therapeutic option in the fertility-preserving treatment of early-stage endometrial cancer in young premenopausal women. However, recurrence rate remains high. Therefore, a close follow-up is mandatory, also in responders. Patients should be informed of limitations and risks of conservative treatment. Yet after completion of family planning, hysterectomy should be performed.
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- 2021
89. Abstract 4376: A correlation of soluble HLA serum levels with clinical data and survival in patients with invasive breast cancer after neoadjuvant treatment
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Christian M. Tegeler, Jonas Rieth, André Koch, Dominik Dannehl, Léa L. Volmer, Sabine Matovina, Markus Hahn, Tobias Engler, Andreas D. Hartkopf, Sara Y. Brucker, Juliane S. Walz, Jonas S. Heitmann, and Annika Nelde
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Cancer Research ,Oncology - Abstract
Invasive breast cancer (IBC) is the most common malignant disease in women worldwide. In recent years, the landscape of treatment options has rapidly evolved. With the success of checkpoint inhibitors in triple negative IBC, immunotherapy has become standard of care highlighting the strength of T cell-based strategies for anti-tumor therapy. Naturally, the targets of T cell-mediated immune responses are represented by short peptides presented on human leukocyte antigen (HLA) molecules. For several years, huge effort has been made to analyze and characterize HLA-presented tumor antigens to further understand anti-tumor immunity and to identify suitable targets for novel immunotherapy approaches. Aside from membrane-bound HLA molecules, soluble HLA-peptide complexes (sHLA) can be found in a variety of body fluids. These molecules are suggested to impact cellular immune responses, but it is still a matter of debate, whether shifts in sHLA levels contribute to disease outcome or are observed as a consequence of disease. Whereas the role of the non-classical sHLA-G in IBC has been studied showing elevated levels in patients compared to a healthy cohort, data on classical sHLA class I molecules is not yet available. Here, we report on sHLA class I serum levels in patients with IBC after neoadjuvant chemotherapy or combined chemotherapy with antibody treatment (n = 52). We observed higher serum levels of sHLA in neoadjuvant-treated IBC patients without histopathological complete response after neoadjuvant therapy (n = 36) compared to healthy volunteers (n = 84). Patients with locally advanced tumors, according to TNM classification, had a tendency towards lower sHLA levels than patients with small size tumors. Furthermore, sHLA levels were decreased in patients with sentinel node or disseminated axillary lymph node metastases compared to non-metastatic patients. Of note, sHLA levels tended to be elevated in patients with Her2-overexpression (based on immunohistochemistry staining and fluorescence in situ hybridization), whereas for histological hormone receptor expression a tendency towards lower sHLA levels in patients with high expression was observed. Furthermore, sHLA levels were reduced in patients with disseminated tumor cells in bone marrow aspiration. No significant difference in sHLA levels were seen in terms of grading of tumor, prevalence of distant metastasis, menopausal status and elevated tumor markers. Interestingly, we observed a tendency to prolonged progression-free survival in patients with high serum concentrations of sHLA, which will be updated with data from additional patients at the AACR meeting. Taken together, these data provides first insights about sHLA class I in patients with IBC after neoadjuvant treatment suggesting an impact of sHLA and T cell-mediated immune surveillance on survival in patients with IBC. Citation Format: Christian M. Tegeler, Jonas Rieth, André Koch, Dominik Dannehl, Léa L. Volmer, Sabine Matovina, Markus Hahn, Tobias Engler, Andreas D. Hartkopf, Sara Y. Brucker, Juliane S. Walz, Jonas S. Heitmann, Annika Nelde. A correlation of soluble HLA serum levels with clinical data and survival in patients with invasive breast cancer after neoadjuvant treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4376.
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- 2023
90. Happy Birthday, Brustzentren!
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Sara Y. Brucker
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General Medicine - Published
- 2023
91. Lymph Node Staging with a Combined Protocol of 18F-FDG PET/MRI and Sentinel Node SPECT/CT: A Prospective Study in Patients with FIGO I/II Cervical Carcinoma
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Sara Y. Brucker, Sergios Gatidis, Samine Sahbai, Matthias Weissinger, Florin-Andrei Taran, Helmut Dittmann, Stefan Kommoss, Christian la Fougère, and Konstantin Nikolaou
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Cervical cancer ,medicine.diagnostic_test ,business.industry ,Sentinel lymph node ,Sentinel node ,Malignancy ,medicine.disease ,Metastasis ,medicine.anatomical_structure ,Biopsy ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Nuclear medicine ,Prospective cohort study ,Lymph node - Abstract
Lymph node metastasis (LNM) is present in a minority of patients with early stages of cervical carcinomas. As conventional imaging including PET/CT has shown limited sensitivity, systematic lymphadenectomies are often conducted for staging purposes. Therefore, the aim of this prospective study was to analyze the impact of 18F-FDG PET/MRI in addition to sentinel lymph node (SLN) biopsy on lymph node (LN) status. Methods: Forty-two women with an initial diagnosis of Federation Internationale de Gynecologie et d’Obstetrique (FIGO) IA–IIB cervical carcinoma were included between March 2016 and April 2019. Each patient underwent preoperative whole-body 18F-FDG PET/MRI and SLN imaging with SPECT/CT after intracervical injection of 99mTc-labeled nanocolloid. Systematic lymphadenectomy and SLN biopsy served as the reference standard. Staging using PET/MRI was performed by nuclear medicine and radiology experts working in consensus. Results: One patient was excluded from surgical staging because of liver metastases newly diagnosed on PET/MRI. The overall prevalence of LNM in the remaining 41 patients was 29.3% (12/41). Five of 12 patients with LNM had solely small metastases with a maximum diameter of 5 mm. The consensus interpretation showed PET/MRI to have a specificity of 100% (29/29; 95% CI, 88.3%–100%) for LNM staging but a low sensitivity, 33.3% (4/12; 95% CI, 12.8%–60.9%). LN size was the most important factor for the detectability of metastases, since only LNMs larger than 5 mm could be identified by PET/MRI (sensitivity, 57.1% for >5 mm and 0% for ≤5 mm). Paraaortic LNM was evaluated accurately in 3 of the 4 patients with paraaortic LN metastasis. SLNs were detectable by SPECT/CT in 82.9% of the patients or 69.0% of the hemipelves. In cases with an undetectable SLN on SPECT/CT, the malignancy rate was considerably higher (31.2% vs. 19.3%). The combination of PET/MRI and SLN SPECT/CT improved the detection of pelvic LNM from 33.3% to 75%. Conclusion:18F-FDG PET/MRI is a highly specific N-staging method and improves LNM detection. Because of the limited sensitivity in frequently occurring small LNMs, PET/MRI should be combined with SLN mapping. The proposed combined protocol helps to decide whether extensive surgical staging is necessary in patients with FIGO I/II cervical cancer.
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- 2021
92. Predictive Clinical Decision Support System with RNN Encoding and Tensor Decoding.
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Yinchong Yang, Peter A. Fasching, Markus Wallwiener, Tanja N. Fehm, Sara Y. Brucker, and Volker Tresp
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- 2016
93. Kinderwunsch bei Müller-Gang-Fehlbildungen – Diagnostik und Therapie
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Andrina Kölle, Katharina Rall, and Sara Y. Brucker
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business.industry ,Medicine ,business - Published
- 2020
94. Electrosurgery and Other Technical Advancements in Minimally Invasive Gynecological Surgery - An Update
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Marcel, Grube, Martin, Weiss, Christina B, Walter, Felix, Neis, Sascha, Hoffmann, Juergen, Andress, Stefan, Kommoss, Sara Y, Brucker, and Bernhard, Krämer
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Gynecologic Surgical Procedures ,Leiomyoma ,Gynecology ,Electrosurgery ,Humans ,Minimally Invasive Surgical Procedures ,Female ,Laparoscopy - Abstract
Electrosurgery in gynecology has changed over the past few decades. The use of energy-based devices, especially in minimally invasive procedures, is extremely important for preparation, short reconvalescence and patient safety. Recently, there have been major advances in energy-based surgical devices that have further shortened OR time and increased patient safety. Although bipolar and monopolar electrosurgery is still very important, the introduction of high-frequency ultrasound in gynecologic surgery has improved cutting and coagulation by lowering thermal damage in the surrounding tissue. Furthermore, new technical inventions have fundamentally changed the treatment of specific diseases. The introduction of ablation in the therapy of uterine fibroids, for example, has made conventional myomectomy no longer necessary in some cases, as necrosis of fibroids can be induced by placing very small thermal probes into the fibroids. Robotic surgery will change the face of gynecological surgery in the near future, as the initial studies could show lower surgical morbidity and faster recovery of patients after robotic-assisted laparoscopy. In this article we provide a short overview of current technical advances, review possible indications as well as limitations, and take a look into the future of minimally invasive surgery in gynecology.
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- 2022
95. Noninvasive Physical Plasma as Innovative and Tissue-Preserving Therapy for Women Positive for Cervical Intraepithelial Neoplasia
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Weiss, Julia Marzi, Matthias B. Stope, Melanie Henes, André Koch, Thomas Wenzel, Myriam Holl, Shannon L. Layland, Felix Neis, Hans Bösmüller, Felix Ruoff, Markus Templin, Bernhard Krämer, Annette Staebler, Jakob Barz, Daniel A. Carvajal Berrio, Markus Enderle, Peter M. Loskill, Sara Y. Brucker, Katja Schenke-Layland, and Martin
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physical atmospheric pressure plasma ,cervical intraepithelial neoplasia (CIN) ,low- and high-grade squamous intraepithelial lesions (LSILs and HSILs) ,Raman imaging ,clinical plasma application - Abstract
(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas “noninvasive physical plasma” (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.
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- 2022
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96. The impact of rehabilitation sport on breast cancer-related lymphoedema and quality of life
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Bettina Boeer, Anna Seller, Birgitt Schoenfisch, Ute krainick-Strobel, Andreas Dietrich, Sara Y. Brucker, Diethelm Wallwiener, Andreas Niess, and Markus Hahn
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Obstetrics and Gynecology ,General Medicine - Abstract
Purpose Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS). Methods Between April and October 2017, a prospective case–control study evaluated the effects of PP compared to a control group. In the paddle group (n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group (n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL. Results The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training—the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time. Conclusion PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.
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- 2022
97. MUC1 (CA27.29) before and after Chemotherapy and Prognosis in High-Risk Early Breast Cancer Patients
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Hanna Huebner, Lothar Häberle, Volkmar Müller, Iris Schrader, Ralf Lorenz, Helmut Forstbauer, Visnja Fink, Fabienne Schochter, Inga Bekes, Sven Mahner, Julia Jückstock, Naiba Nabieva, Andreas Schneeweiss, Hans Tesch, Sara Y. Brucker, Jens-Uwe Blohmer, Tanja N. Fehm, Georg Heinrich, Mahdi Rezai, Matthias W. Beckmann, Peter A. Fasching, Wolfgang Janni, and Brigitte Rack
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Cancer Research ,Oncology ,ddc:610 ,early breast cancer ,tumor marker ,chemotherapy ,anthracycline ,taxane ,MUC1 ,CA27.29 ,CA15-3 - Abstract
Simple Summary CA27.29 (MUC1) is a well described biomarker for prediction of prognosis and treatment efficacy. CA27.29 is mainly evaluated in the preoperative setting. However, testing of postoperative levels and additional assessment after chemotherapy might be more informative for analyzing the usefulness of CA27.29 in relation to the efficacy of chemotherapy. Thus, both pre- and post-chemotherapy values were assessed from patients enrolled in the breast cancer SUCCESS-A trial. Pre-chemotherapy assessment was associated with disease-free survival. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Furthermore, it was shown that post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy assessment. In conclusion, this indicates that pre- and post-chemotherapy values do not provide additional information. However, pre-chemotherapy CA27.29 could be a suitable tool to identify a group with unfavorable prognosis among node-positive patients. Abstract Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.
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- 2022
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98. Noninvasive Physical Plasma as Innovative and Tissue-Preserving Therapy for Women Positive for Cervical Intraepithelial Neoplasia
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Julia, Marzi, Matthias B, Stope, Melanie, Henes, André, Koch, Thomas, Wenzel, Myriam, Holl, Shannon L, Layland, Felix, Neis, Hans, Bösmüller, Felix, Ruoff, Markus, Templin, Bernhard, Krämer, Annette, Staebler, Jakob, Barz, Daniel A, Carvajal Berrio, Markus, Enderle, Peter M, Loskill, Sara Y, Brucker, Katja, Schenke-Layland, and Martin, Weiss
- Abstract
(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas "noninvasive physical plasma" (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.
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- 2022
99. Feasibility of Adjuvant Treatment with Abemaciclib—Real-World Data from a Large German Breast Center
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Hartkopf, Dominik Dannehl, Lea L. Volmer, Martin Weiss, Sabine Matovina, Eva-Maria Grischke, Ernst Oberlechner, Anna Seller, Christina B. Walter, Markus Hahn, Tobias Engler, Sara Y. Brucker, and Andreas D.
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breast cancer ,oncology ,CDK 4/6 ,systemic therapy ,monarchE ,abemaciclib - Abstract
Abemaciclib significantly improves invasive disease-free survival when combined with endocrine therapy in clinical high-risk patients with HR+/Her2− early breast cancer (eBC). The objective of the following study was to model how many patients with eBC would be available for adjuvant treatment with abemaciclib in a real-world setting. Patients that underwent complete surgical treatment for eBC between January 2018 and December 2020 in a large single-center university hospital in Germany were eligible. Descriptive statistics were used to describe the patient population that could benefit from abemaciclib according to the inclusion criteria of monarchE. Of 1474 patients with eBC, 1121 (76.1%) had a HR+/Her2− subtype. Of these, 217 (19.4%) fulfilled the monarchE inclusion criteria. Within patients that fulfilled the monarchE inclusion criteria, 48.9% received no adjuvant or neoadjuvant chemotherapy. Thus, in a real-world situation, fewer patients will be pretreated with chemotherapy than was the case in monarchE. Breast care units are facing a significant patient burden, since the 2-year abemaciclib therapy requires regular monitoring of toxicities. Specific care concepts to strengthen therapy adherence as well as further studies to deescalate adjuvant systemic treatment and individualize CDK 4/6 inhibitor therapy are therefore needed.
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- 2022
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100. Sequencing for an interdisciplinary molecular tumor board in patients with advanced breast cancer: experiences from a case series
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Andreas D. Hartkopf, Florian Battke, Eva-Maria Grischke, Sara Y. Brucker, Marion Klaumünzer, André Koch, Saskia Biskup, Martin Schulze, Florin-Andrei Taran, and Christina B. Walter
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Advanced breast ,actionable mutations ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Quality of life ,Internal medicine ,medicine ,In patient ,genetics ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,next-generation sequencing ,business ,Research Paper - Abstract
Purpose High throughput panel sequencing to tailor therapy in precision oncology promises to improve outcome in patients with metastatic breast cancer. However, data that clearly show any benefit from such an approach is still pending. Materials and methods We performed a retrospective analysis of advanced breast cancer patients that underwent panel sequencing for suggestion of target related drugs. We aimed to (i) determine the frequency of actionable mutations per patient and to (ii) assess the clinical impact of results on treatment options. Results A total of 52 patients underwent panel sequencing of archived tumor tissue. Every sample showed at least one affected gene, accounting for actionable mutations in 45 of 52 patients (87%). New treatment options that would not have been used as indicated by standard predictive markers (such as hormonal receptor status or HER2-status) were found in 22 of 52 patients (42%). We detected therapeutic relevant pathogenic germline variants in 9,6% (5/52) of the patients. Conclusions Using a high throughput-panel sequencing approach to identify actionable mutations in patients with metastatic breast cancer, we identified potential target-related treatment options in a large proportion of our patients, some of which would not have been considered without this data. Prospective clinical trials with compounds targeting the identified actionable mutations are needed to determine which treatments can indeed improve survival or quality of life by limiting exposure to ineffective drugs in advanced breast cancer.
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- 2020
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