56 results on '"Christine Mau"'
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2. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer
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C.E. Geyer, J.E. Garber, R.D. Gelber, G. Yothers, M. Taboada, L. Ross, P. Rastogi, K. Cui, A. Arahmani, G. Aktan, A.C. Armstrong, M. Arnedos, J. Balmaña, J. Bergh, J. Bliss, S. Delaloge, S.M. Domchek, A. Eisen, F. Elsafy, L.E. Fein, A. Fielding, J.M. Ford, S. Friedman, K.A. Gelmon, L. Gianni, M. Gnant, S.J. Hollingsworth, S.-A. Im, A. Jager, Ó. Þ Jóhannsson, S.R. Lakhani, W. Janni, B. Linderholm, T.-W. Liu, N. Loman, L. Korde, S. Loibl, P.C. Lucas, F. Marmé, E. Martinez de Dueñas, R. McConnell, K.-A. Phillips, M. Piccart, G. Rossi, R. Schmutzler, E. Senkus, Z. Shao, P. Sharma, C.F. Singer, T. Španić, E. Stickeler, M. Toi, T.A. Traina, G. Viale, G. Zoppoli, Y.H. Park, R. Yerushalmi, H. Yang, D. Pang, K.H. Jung, A. Mailliez, Z. Fan, I. Tennevet, J. Zhang, T. Nagy, G.S. Sonke, Q. Sun, M. Parton, M.A. Colleoni, M. Schmidt, A.M. Brufsky, W. Razaq, B. Kaufman, D. Cameron, C. Campbell, A.N.J. Tutt, Paul Sevelda, Ferdinand Haslbauer, Monika Penzinger, Leopold Öhler, Christoph Tinchon, Richard Greil, Sonja Heibl, Rupert Bartsch, Viktor Wette, Christian F. Singer, Claudia Pasterk, Ruth Helfgott, Gunda Pristauz-Telsnigg, Herbert Stöger, Angsar Weltermann, Daniel Egle, Irene Thiel, David Fuchs, Holger Rumpold, Kathrin Strasser-Weippl, Beate Rautenberg, Volkmar Müller, Marcus Schmidt, Stefan Paepke, Mustafa Aydogdu, Christoph Thomssen, Joachim Rom, Christine Mau, Peter Fasching, Uwe-Jochen Göhring, Thorsten Kühn, Stefanie Noeding, Sherko Kümmel, John Hackmann, Elmar Stickeler, Abhishek Joshi, Joanna Dewar, Michael Friedlander, Kelly-Anne Phillips, Yoland Antill, Natasha Woodward, Ehtesham Abdi, Susan Tiley, Mathew George, David Boadle, Annabel Goodwin, Andre van der Westhuizen, George Kannourakis, Nicholas Murray, Nicole McCarthy, Judith Kroep, Maaike de Boer, Joan Heijns, Agnes Jager, Franciscus Erdkamp, Sandra Bakker, Gabe S. Sonke, Amer Sami, John Mackey, Catherine Prady, Andrea Eisen, Christine Desbiens, Erica Patocskai, Cristiano Ferrario, Karen Gelmon, Louise Bordeleau, Haji Chalchal, Saroj Niraula, null ido wolf, Elżbieta Senkus, François Duhoux, null Randal d’Hondt, Sylvie Luce, Daphné t’Kint de Roodenbeke, Konstantinos Papadimitriou, Marleen Borms, Claire Quaghebeur, William Jacot, Etienne Brain, Laurence Venat-Bouvet, Alain Lortholary, Zbigniew Nowecki, Fátima Cardoso, Richard Hayward, Santiago Bella, Mauricio Fernández Lazzaro, Norma Pilnik, Luis E. Fein, Cesar Blajman, Guillermo Lerzo, Mirta Varela, Juan Jose Zarba, Diego Kaen, Maria Victoria Constanzo, Joke Tio, Wulf Siggelkow, Christian Jackisch, Eva Maria Grischke, Dirk Zahm, Sara Tato-Varela, Sabine Schmatloch, Peter Klare, Andrea Stefek, Kerstin Rhiem, Oliver Hoffmann, Mustafa Deryal, Isolde Gröll, Peter Ledwon, Christoph Uleer, Petra Krabisch, Jochem Potenberg, Maren Darsow, Tjoung-Won Park-Simon, Heinz-Gert Höffkes, Till-Oliver Emde, Gerd Graffunder, Oliver Tomé, Dirk Forstmeyer, Jürgen Terhaag, Christoph Salat, Karin Kast, Steffi Weniger, Carsten Schreiber, Bernhard Heinrich, Max Dieterich, Michaela Penelope Wüllner, Raquel Andrés Conejero, José Ángel García Sáenz, Lourdes Calvo Martinez, Angels Arcusa Lanza, Serafín Morales Murillo, Fernando Henao Carrasco, Salvador Blanch Tormo, Isabel Álvarez López, Juan Ignacio Delgado Mingorance, Elena Álvarez Gomez, Marta Santisteban, Josefina Cruz Jurado, Vanesa Quiroga, Manuel Ruiz Borrego, Eduardo Martínez de Dueñas, Jose Enrique Alés Martínez, Juan De la Haba, Noelia Martínez Jañez, Álvaro Rodríguez Lescure, Antonio Antón Torres, Gema Llort Crusades, Santiago González-Santiago, Antonia Marquez Aragones, Ana Laura Ortega, Agusti Barnadas Molins, José Ignacio Chacón López-Muñiz, Miguel Martín Jiménez, Ana Santaballa Bertrán, César Rodríguez, Lucía González Cortijo, Elisabetta Cretella, Laura Cortesi, Enzo Maria Ruggeri, Claudio Verusio, Stefania Gori, Andrea Bonetti, Anna Maria Mosconi, Oskar Johannsson, Guy Jerusalem, Patrick Neven, Tünde Nagy, Graziella Pinotti, Marco A. Colleoni, Antonio Bernardo, Lorenzo Gianni, Eraldo Bucci, Laura Biganzoli, Konstantin Dedes, Urban Novak, Khalil Zaman, Jeremy Braybrooke, Matthew Winter, Daniel Rea, Muireann Kelleher, Sophie Barrett, Stephen Chan, Tamas Hickish, Jane Hurwitz, John Conibear, Apurna Jegannathen, Marina Parton, Andrew Tutt, Rozenn Allerton, Annabel Borley, Anne Armstrong, Ellen Copson, Nicola Levitt, Jean Abraham, Timothy Perren, Rebecca Roylance, Kazushige Ishida, Tatsuya Toyama, Norikazu Masuda, Junichiro Watanabe, Eriko Tokunaga, Takayuki Kinoshita, Yoshiaki Rai, Masahiro Takada, Yasuhiro Yanagita, Rikiya Nakamura, Takahiro Nakayama, Yasuto Naoi, Hiroji Iwata, Seigo Nakamura, Masato Takahashi, Kenjiro Aogi, Koichiro Tsugawa, Hirofumi Mukai, Toshimi Takano, Akihiko Osaki, Nobuaki Sato, Hideko Yamauchi, Yutaka Tokuda, Mitsuya Ito, Takeki Sugimoto, Shakeela W. Bahadur, Patricia A. Ganz, Min J. Lu, Monica M. Mita, James Waisman, Jonathan A. Polikoff, Melinda L. Telli, Samantha A. Seaward, J. Marie Suga, Lara N. Durna, Jennifer Fu Carney, Alex Menter, Ajithkumar Puthillath, Nitin Rohatgi, James H. Feusner, Kristie A. Bobolis, Peter D. Eisenberg, Derrick Wong, Virginia F. Borges, Alexander T. Urquhart, Erin W. Hofstatter, Edward C. McCarron, Claudine Isaacs, Pia Herbolsheimer, Ramya Varadarajan, Adam Raben, Ruby Anne E. Deveras, Frances Valdes-Albini, Reshma L. Mahtani, Jane L. Meisel, Bradley T. Sumrall, Cheryl F. Jones, Samuel N. Ofori, Kenneth N.M. Sumida, Mark Karwal, Deborah W. Wilbur, (Joe) Singh, David M. Spector, John Schallenkamp, Douglas E. Merkel, Shelly S. Lo, Pam G. Khosla, Massimo Cristofanilli, Lisa Flaum, Kent F. Hoskins, Melody A. Cobleigh, Elyse A. Lambiase, Olwen M. Hahn, Ira A. Oliff, Bryan A. Faller, James L. Wade, Nafisa D. Burhani, Amaryllis Gil, Harvey E. Einhorn, Anna M.V. Storniolo, Brian K. Chang, Maitri Kalra, Erwin L. Robin, Bilal Ansari, Priyanka Sharma, Shaker R. Dakhil, Richard L. Deming, John T. Cole, David S. Hanson, Augusto C. Ochoa, Judy E. Garber, Harvey Zimbler, Deborah K. Armstrong, Katherine H.R. Tkaczuk, David A. Riseberg, Brian M. O'Connor, Thomas H. Openshaw, Dana Zakalik, Cynthia M. Vakhariya, Anne F. Schott, Michael S. Simon, Thomas J. Doyle, Tareq Al Baghdadi, Amy VanderWoude, Patrick J. Flynn, Richard T. Zera, Bret E.B. Friday, Kathryn J. Ruddy, Ron Smith, null Ademuyiwa, Foluso Olabisi, Robert Ellis, Jay W. Carlson, null Marchello, Benjamin T, Edward A. Levine, Paul K. Marcom, Cameron B. Harkness, Antoinette R. Tan, William J. Charles, Charles S. Kuzma, Shonda Asaad, James E. Radford, Preston D. Steen, Madhu Unnikrishnan, Grant R. Seeger, Kirsten M.H. Leu, Mehmet S. Copur, Ralph J. Hauke, Gamini S. Soori, Bradley A. Arrick, Jennifer G. Reeder, Deborah L. Toppmeyer, Zoneddy R. Dayao, Sylvia Adams, Eleni Andreopoulou, Magnuson Allison, Jesus D. Anampa Mesias, Ruby Sharma, Bhuvaneswari Ramaswamy, Aaron T. Gerds, Robert R. Shenk, Howard M. Gross, Shruti Trehan, Wajeeha Razaq, Abdul H. Mansoor, Christie J. Hilton, Adam M. Brufsky, Chanh Huynh, Nabila Chowdhury, Susan M. Domchek, Elin R. Sigurdson, Terrence P. Cescon, Marc A. Rovito, Albert S. DeNittis, Victor G. Vogel, Thomas B. Julian, L.E. Boyle, Luis Baez-Diaz, Frank J. Brescia, John E. Doster, Robert D. Siegel, Lucas Wong, Tejal Patel, Julie R. Nangia, Catherine A. Jones, George M. Cannon, Harry D. Bear, Hetal Vachhani, Mary Wilkinson, Marie E. Wood, Fengting Yan, Xingwei Sui, Carol M. van Haelst, Jennifer M. Specht, Ying Zhuo, Rubina Qamar, Matthew L. Ryan, Abigail Stockham, Shamsuddin Virani, Arlene A. Gayle, Steven J. Jubelirer, Sobha Kurian, Mohamad A. Salkeni, Niklas Loman, Barbro Linderholm, Gustav Silander, Anna-Lotta Hallbeck, Anna von Wachenfeldt Väppling, Elsa Curtit, Catarina Cardoso, Sofia Braga, Miguel Abreu, Mafalda Casa-Nova, Mónica Nave, Eva María Ciruelos Gil, Judith Balmaña Gelpi, Adela Fernández Ortega, Josep Gumà Padró, Begoña Bermejo de las Heras, María González Cao, Juan Cueva Bañuelos, Jesús Alarcon Company, Gemma Viñas Villaró, Laura García Estevez, Jens Huober, Steffi Busch, Tanja Fehm, Antje Hahn, Andrea Grafe, Thomas Noesselt, Thomas Dewitz, Harald Wagner, Christina Bechtner, Michael Weigel, Hans-Christian Kolberg, Thomas Decker, Jörg Thomalla, Tobias Hesse, Nadia Harbeck, Jan Schröder Jens-Uwe Blohmer, Marc Wolf Sütterlin, Renske Altena, Chang-Fang Chiu, Shin-Cheh Chen, Ming-Feng Hou, Yuan-Ching Chang, Shang-Hung Chen, Shou-Tung Chen, Chiun-Sheng Huang, Dah-Cherng Yeh, Jyh-Cherng Yu, Ling-Ming Tseng, Wei-Pang Chung, Audrey Mailliez, Thierry Petit, Suzette Delaloge, Christelle Lévy, Philippe Dalivoust, Jean-Marc Extra, Marie-Ange Mouret-Reynier, Anne-Claire Hardy-Bessard, Hélène Simon, Tiffenn L'Haridon, Alice Mege, Sylvie Giacchetti, Camille Chakiba-Brugere, Alain Gratet, Virginie Pottier, Jean-Marc Ferrero, Isabelle Tennevet, Christophe Perrin, Jean-Luc Canon, Sofie Joris, Zhimin Shao, Binghe Xu, ZeFei Jiang, Qiang Sun, Kunwei Shen, Da Pang, Jin Zhang, Shui Wang, Hongjian Yang, Ning Liao, Hong Zheng, Peifen Fu, Chuangui Song, Yongsheng Wang, Zhimin Fan, Cuizhi Geng, Olivier Tredan, László Landherr, Bella Kaufman, Rinat Yerushalmi, Beatrice Uziely, Pierfranco Conte, Claudio Zamagni, Giampaolo Bianchini, Michelino De Laurentiis, Carlo Tondini, Vittorio Gebbia, Mariangela Ciccarese, Tomasz Sarosiek, Jacek Mackiewicz, Anna Słowińska, Ewa Kalinka, Tomasz Huzarski, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Jee Hyun Kim, Keun Seok Lee, Yeon Hee Park, Kyoung Eun Lee, Yee Soo Chae, Eun Kyung Cho, Institut Català de la Salut, [Geyer CE Jr] NRG Oncology/NSABP Foundation, Pittsburgh, USA. Department of Medicine, UPMC Hillman Cancer Center, Pittsburgh, USA. [Garber JE] Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. [Gelber RD] Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. Harvard T.H. Chan School of Public Health, Boston, USA. Frontier Science Foundation, Boston, USA. [Yothers G] NRG Oncology/NSABP Foundation, Pittsburgh, USA. Department of Biostatistics, University of Pittsburgh, Pittsburgh, USA. [Taboada M] Oncology Biometrics Department, AstraZeneca, Macclesfield, UK. [Ross L] Department of Data Management, Frontier Science (Scotland), Kincraig, Scotland, UK. [Balmaña J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Medical Oncology, Public Health, Virology, Department of Psychology, Education and Child Studies, Internal Medicine, General Practice, and Child and Adolescent Psychiatry / Psychology
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Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Medicaments antineoplàstics - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Breast Neoplasms ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,olaparib ,Article ,breast cancer ,SDG 3 - Good Health and Well-being ,BRCA1/2 ,células::células germinativas [ANATOMÍA] ,Humans ,Other subheadings::/therapeutic use [Other subheadings] ,Cells::Germ Cells [ANATOMY] ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Otros calificadores::/uso terapéutico [Otros calificadores] ,BRCA1 Protein ,PARP inhibition ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,adjuvant therapy ,Hematology ,Cèl·lules germinals ,Germ Cells ,Oncology ,Mama - Càncer - Tractament ,Phthalazines ,Female ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] - Abstract
Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.
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- 2022
3. Meningioma Growth in Transsexual Patients in the Setting of Gender-Reaffirming Estrogen Therapy
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Christine Mau, Annika Mascarenhas, Gavin Lockard, Jonah Gordon, Adam Alayli, Craig Hatchwell, Adam Wells, and Stephen Santoreneos
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- 2023
4. Outcomes of Surgical Clipping of Recurrent Cerebral Aneurysms after Endovascular Treatment (EVT)
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Seevakan Chidambaram, Christine Mau, Sarah Howson, Stephanie Plummer, Aye Aye Gyi, Rebecca Scroop, and Amal Abou-Hamden
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- 2023
5. Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study
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Ronald E Warnick, Monica Mureb, Piero Picozzi, Samir Patel, Roman Liscak, Leonard Tuanquin, Nuria Martinez-Moreno, L. Dade Lunsford, Herwin Speckter, Brad E. Zacharia, Joshua D Hack, Christine Mau, Gabriel Zada, Douglas Kondziolka, Alexander R Haber, Luca Attuati, Dale Ding, Tomas Chytka, Huai-Che Yang, Eric L. Chang, Roberto Martinez-Alvarez, Hideyuki Kano, Love Buch, Jason P. Sheehan, Cheng-Chia Lee, David E. Arsanious, I. Jonathan Pomeraniec, Christopher P. Cifarelli, Michel Maillet, Kimball Sheehan, Kenneth E. Bernstein, David Mathieu, Akiyoshi Ogino, Jacob Shteinhart, Hao Long, Svetlana Kvint, Zhiyuan Xu, Ben A Strickland, Mary Lee Vance, and Darrah Sheehan
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Adenoma ,Pituitary stalk ,medicine.medical_specialty ,Pituitary gland ,business.industry ,medicine.medical_treatment ,Radiography ,Urology ,General Medicine ,Hypopituitarism ,Radiosurgery ,medicine.disease ,Treatment Outcome ,medicine.anatomical_structure ,Pituitary adenoma ,Hypothalamus ,medicine ,Humans ,Endocrine system ,Pituitary Neoplasms ,business ,Follow-Up Studies ,Retrospective Studies - Abstract
OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.
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- 2022
6. Myxopapillary Ependymoma with Anaplastic Features: A Case Series and Review of the Literature
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Oliver D. Mrowczynski, Dawit Aregawi, Elias Rizk, Christine Mau, Ganesh Shenoy, Vladimir Khristov, Cunfeng Pu, and Charles S. Specht
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Adult ,Male ,Sacrum ,medicine.medical_specialty ,Myxopapillary ependymoma ,Adolescent ,Resection ,Young Adult ,Presacral space ,medicine ,Humans ,Spinal Cord Neoplasms ,Series (stratigraphy) ,business.industry ,Lumbosacral Region ,Solid mass ,Middle Aged ,Ki-67 Antigen ,Ependymoma ,Lumbar mass ,Female ,Surgery ,Neurology (clinical) ,Radiology ,business ,Lumbosacral joint - Abstract
Background Myxopapillary ependymomas (MPE) with anaplastic features are rarely reported with only 21 cases identified to date, and long-term recurrence is rarely presented. The purpose of this case series is to expand understanding of this disease by describing three unique cases, including two that arose from myxopapillary ependymoma after a prolonged clinical course. Methods A review of literature and three cases of MPE with anaplastic features are described. Results Patient 1 is a 13-year-old male who presented with an avidly enhancing intradural lumbar mass. Upon gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and a MIB-1 (Ki-67) index of 12%. Patient 2 is a female who initially presented at age 22 with a lumbosacral tumor that treated with surgery and radiation. A recurrent tumor was resected at age 24. Twenty-six years later, at age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending into the presacral space and Ki-67 index of 8%. This was treated with complete resection. Patient 3 is a male who initially presented at age 35 with a lower thoracic, upper lumbar mass at L2 extending into the sacrum. Following resection and radiation, a metastatic focus followed an indolent course until causing pain at the age of 48. The Ki-67 index was 16%. Conclusions The presented cases of MPE with anaplastic features make a total of 24 cases on record in the medical literature and demonstrate two examples of late recurrence.
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- 2022
7. Risk factors in implant-based mesh supported breast reconstruction - Pro Bra trial
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Stefan Paepke, Evelyn Klein, Andree Faridi, Christine Ankel, Anette Meire, Claudia Gerber-Schäfer, Kristin Baumann, Jens-Uwe Blohmer, Christine Mau, Elke Nolte, Mathias Sander, and Marc Thill
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Oncology ,Surgery ,General Medicine - Published
- 2023
8. Malignant spindle cell tumors of the posterior fossa in children: case series and review of management
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Elias Rizk, Sarah McNutt, Shreela Natarajan, Charles S. Specht, Mark Iantosca, Cynthia Lawson, Christine Mau, and Michael J. Gigliotti
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Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Infratentorial Neoplasms ,Soft Tissue Neoplasms ,Sarcoma, Ewing ,Meningeal Neoplasms ,Humans ,Medicine ,Child ,Chemotherapy ,business.industry ,Mesenchymal stem cell ,Not Otherwise Specified ,Sarcoma ,Multimodal therapy ,General Medicine ,Immunotherapy ,medicine.disease ,Radiation therapy ,Treatment Outcome ,Female ,Radiology ,Spindle cell sarcoma ,business - Abstract
OBJECTIVE The WHO Classification of Tumours of the Central Nervous System (2016) classifies nonmeningothelial malignant spindle cell tumors involving the extraaxial tissues of the posterior fossa as melanocytic tumors and malignant mesenchymal tumors (sarcomas). The objective of this study was to conduct a review of the literature pertaining to the management strategies of posterior fossa malignant spindle cell tumors in the pediatric population. METHODS The authors performed an institutional search of their pathology database for patients younger than 18 years of age who presented with posterior fossa malignant spindle cell tumors. A literature review was also performed using the PubMed database, with “posterior fossa” or “spindle cell tumors” or “Ewing sarcoma” or “high-grade” or “spindle cell sarcoma” or “leptomeningeal melanocytoma” as keywords. The database search was restricted to pediatric patients (age ≤ 18 years). Parameters reported from the literature review included patient age, tumor location, presenting symptoms, treatment modalities (resection, chemotherapy, and/or radiotherapy), leptomeningeal spread at or after the time of treatment, and follow-up length and resulting outcome. RESULTS The authors report 3 rare cases of posterior fossa malignant spindle cell tumors, including Ewing sarcoma in a 13-year-old male; high-grade spindle cell sarcoma, not otherwise specified in a 10-year-old male; and primary leptomeningeal melanocytoma in a 16-year-old female. All 3 patients underwent resection and radiotherapy and either chemotherapy or targeted immunotherapy. At the last follow-up, all patients were alive with either resolution or stable disease. CONCLUSIONS A review of these 3 cases and the existing literature support managing patients with intracranial malignant spindle cell tumors with multimodal therapy that can include a combination of resection, radiotherapy, and chemotherapy or immunotherapy to prolong progression-free and overall survival.
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- 2021
9. Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study
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Jaromir Hanuska, Love Buch, Jennifer L. Peterson, Jason P. Sheehan, Adomas Bunevicius, Akiyoshi Ogino, Anne Marie Langlois, Ronald E Warnick, Hideyuki Kano, James McInerney, Gabriel Zada, Anissa Saylany, L. Dade Lunsford, Catherine Caldwell, Huai-Che Yang, Mohand Suleiman, Roberto Martínez Álvarez, Cheng-Chia Lee, Christine Mau, Daniel M. Trifiletti, Brad E. Zacharia, Samir Patel, Leonard Tuanquin, David Mathieu, Ben A. Strickland, John Y K Lee, Eric L. Chang, Nuria Martinez Moreno, and Roman Liscak
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Medulloblastoma ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Planning target volume ,Radiation induced ,General Medicine ,medicine.disease ,Cranial radiation ,Radiosurgery ,03 medical and health sciences ,Safety profile ,0302 clinical medicine ,Cranial Irradiation ,030220 oncology & carcinogenesis ,parasitic diseases ,Medicine ,Progression-free survival ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVE Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs. METHODS From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS. RESULTS Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4–195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3–45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028–65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS. CONCLUSIONS SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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- 2021
10. How enhancers regulate wavelike gene expression patterns: Novel enhancer prediction and live reporter systems identify an enhancer associated with the arrest of pair-rule waves in the short-germ beetleTribolium
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Christine Mau, Heike Rudolf, Frederic Strobl, Benjamin Schmid, Timo Regensburger, Ralf Palmisano, Ernst Stelzer, Leila Taher, and Ezzat El-Sherif
- Abstract
A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called ‘enhancers’. Much of our models of how enhancers work rely on the assumption that genes are activatedde novoas stable domains across embryonic tissues. Such view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of theDrosophilaembryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expressions in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetleTribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here we establish the AP patterning of the short-germ beetleTriboliumas a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system inTriboliumbased on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered severalTriboliumenhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expressions (that we call ‘dynamic enhancers’) and enhancers that stabilizes gene expressions (that we call ‘static enhancers’).
- Published
- 2022
11. Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection
- Author
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Sergio D. Bergese, Alberto A. Uribe, Alexandre B. Todeschini, Grace Musto, Christine Mau, Mohit Sharma, Tumul Chowdhury, Kristen Gray, Derek S. Tsang, Lashmi Venkatraghavan, Catherine Caldwell, Seyed A Mansouri, Saranya Kakumanu, Sarah McNutt, Noa Farou, Oliver Bucher, Gelareh Zadeh, Emad Al Azazi, Casey Ryan, and Patrick Bergquist
- Subjects
medicine.medical_treatment ,Sedation ,Anesthesia, General ,Interquartile range ,Glioma ,medicine ,Humans ,Prospective Studies ,Wakefulness ,Craniotomy ,Retrospective Studies ,Brain Neoplasms ,business.industry ,Hazard ratio ,Retrospective cohort study ,Perioperative ,medicine.disease ,Radiation therapy ,Anesthesiology and Pain Medicine ,Anesthesia ,Surgery ,Neurology (clinical) ,medicine.symptom ,business - Abstract
BACKGROUND High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown. METHODS This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay. RESULTS A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P
- Published
- 2021
12. Sellar Atypical Teratoid/Rhabdoid Tumors (AT/RT): A Systematic Review and Case Illustration
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Kimberly Major, Lekhaj C Daggubati, Christine Mau, Brad Zacharia, Michael Glantz, and Cunfeng Pu
- Subjects
General Engineering - Abstract
Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs.A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms "sellar" and "atypical teratoid/rhabdoid tumors", following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens.Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months;Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.
- Published
- 2022
13. Targeting IL-13Rα2 for effective treatment of malignant peripheral nerve sheath tumors in mouse models
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James R. Connor, A. B. Madhankumar, Alexandre J. Bourcier, Christine Mau, Darren Wolfe, Elias Rizk, Oliver D. Mrowczynski, Kimberly Harbaugh, Becky Slagle-Webb, Stephan B. Abramson, Russell Payne, and Ganesh Shenoy
- Subjects
0303 health sciences ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Intratumoral Therapy ,General Medicine ,medicine.disease ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,030220 oncology & carcinogenesis ,Toxicity ,Cancer research ,Medicine ,Pseudomonas exotoxin ,Cytotoxic T cell ,business ,Receptor ,030304 developmental biology - Abstract
OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that harbor a high potential for metastasis and have a devastating prognosis. Combination chemoradiation aids in tumor control and decreases tumor recurrence but causes deleterious side effects and does not extend long-term survival. An effective treatment with limited toxicity and enhanced efficacy is critical for patients suffering from MPNSTs.METHODSThe authors recently identified that interleukin-13 receptor alpha 2 (IL-13Rα2) is overexpressed on MPNSTs and could serve as a precision-based target for delivery of chemotherapeutic agents. In the work reported here, a recombinant fusion molecule consisting of a mutant human IL-13 targeting moiety and a point mutant variant of Pseudomonas exotoxin A (IL-13.E13 K-PE4E) was utilized to treat MPNST in vitro in cell culture and in an in vivo murine model.RESULTSIL-13.E13 K-PE4E had a potent cytotoxic effect on MPNST cells in vitro. Furthermore, intratumoral administration of IL-13.E13 K-PE4E to orthotopically implanted MPNSTs decreased tumor burden 6-fold and 11-fold in late-stage and early-stage MPNST models, respectively. IL-13.E13 K-PE4E treatment also increased survival by 23 days in the early-stage MPNST model.CONCLUSIONSThe current MPNST treatment paradigm consists of 3 prongs: surgery, chemotherapy, and radiation, none of which, either singly or in combination, are curative or extend survival to a clinically meaningful degree. The results presented here provide the possibility of intratumoral therapy with a potent and highly tumor-specific cytotoxin as a fourth treatment prong with the potential to yield improved outcomes in patients with MPNSTs.
- Published
- 2019
14. Pituitary Metastasis From Urothelial Carcinoma: A Case Report and Review of the Diagnosis and Treatment of Pituitary Metastases
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David Bailey, Christine Mau, and Brad E. Zacharia
- Subjects
medicine.medical_specialty ,Palsy ,business.industry ,Urology ,medicine.medical_treatment ,Neurosurgery ,General Engineering ,pituitary adenoma ,Disease ,medicine.disease ,sellar metastasis ,Radiosurgery ,Metastasis ,Oncology ,Pituitary adenoma ,Diabetes insipidus ,medicine ,pituitary metastasis ,brain metastasis ,Radiology ,business ,Lung cancer ,urothelial carcinoma ,Brain metastasis - Abstract
The sellar and parasellar regions are a rare site of brain metastasis, most commonly from breast and lung cancer. Pituitary metastasis (PM) often presents as the first sign of metastatic disease but may herald early disseminated cancer. The diagnosis of PM requires differentiation from a benign pituitary adenoma. Although this may be proven definitively via surgical biopsy, a constellation of clinical findings including oculomotor palsy, visual disturbances, retroorbital pain, and diabetes insipidus is more suggestive of PM. Imaging is neither sensitive nor specific for differentiation but may inform the broader clinical picture. Due to its rarity, treatment guidelines for PM lack consensus, often including a mixture of radiation and surgery. Gross resection is challenging because of the vascular, invasive nature of these lesions. Stereotactic radiosurgery may be used to good effect either alone or in addition to resection. Even with treatment, the prognosis is poor. In this article, we present the third reported case of urothelial carcinoma metastasis to the pituitary. In addition, we review the clinical presentation, diagnosis, and treatment options including surgical resection and radiosurgery.
- Published
- 2021
15. Extracranial medulloepithelioma: a review of the literature
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David Bailey, Christine Mau, Elizabeth Finchea, Christina Toepke, and Elias Rizk
- Subjects
Male ,Pediatrics, Perinatology and Child Health ,Proton Therapy ,Humans ,Neuroectodermal Tumors, Primitive ,Neurology (clinical) ,General Medicine ,Child - Abstract
Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region of the cerebral hemispheres or the ciliary body of the eye. Even rarer still is the extracranial manifestation of medulloepithelioma with only 12 cases reported to date. Our purpose is to report a case of an intradural, extra-medullary medulloepithelioma and review the limited literature about diagnosis and treatment of this extremely rare pathology.PubMed was queried using search terms "peripheral medulloepithelioma" and "pre-sacral medulloepithelioma." Medulloepitheliomas which were intraocular or occurred in reproductive organs were excluded. Patients' age, sex, the symptomatic period prior to diagnosis, primary tumor site, stage, treatment regimen, pathologic description, and survival outcomes were collected.We present a case of extracranial medulloepithelioma in an 8-year-old male. Morphology of the neoplasm was representative of medulloepithelioma but there was no amplification of C19MC. Additionally, the neoplasm stained positive for CD99. Twelve other cases of extracranial medulloepithelioma were found in literature review.The rarity of extracranial medulloepithelioma makes for a challenging diagnosis. Designing an optimal treatment strategy is difficult because of a scarcity of cases and wide variety in locations and treatments. Our case provides an example of treatment including resection, intense induction chemotherapy, consolidation with high-dose chemotherapy and stem cell rescue, craniospinal proton radiation therapy, and metronomic chemotherapy.
- Published
- 2021
16. Arachnoiditis Ossificans in the Thoracic Spine With Associated Cyst and Syringomyelia: A Rare, Intraoperative Finding Complicating Dural Opening
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John P. Kelleher, Elias Rizk, Christine Mau, and David Bailey
- Subjects
medicine.medical_specialty ,business.industry ,General Engineering ,Neurosurgery ,medicine.disease ,spine ,syringomyelia ,Myelopathy ,Cerebrospinal fluid ,arachnoiditis ,Arachnoid cyst ,arachnoiditis ossificans ,arachnoid cyst ,medicine ,Cyst ,Syrinx (medicine) ,Radiology ,Arachnoiditis ,business ,Syringomyelia ,Calcification - Abstract
Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia secondary to chronic inflammation. AO may present with debilitating myelopathy secondary to nerve root compression, making it distinct from spinal calcification commonly seen with aging. AO is extremely rare, having been reported less than 100 times, most commonly in the thoracic spine. Even rarer still, AO has been associated with syringomyelia and arachnoid cyst because of associated cerebrospinal fluid (CSF) flow disruption. In this report, we describe a case of AO that presented with right shoulder pain, right-hand numbness, and bilateral lower extremity fatigue who had syringomyelia and arachnoid cyst discovered on MRI imaging. When brought to the operating room for syrinx shunting and cyst fenestration the dural opening was complicated by severe calcification and a diagnosis of AO was made. The patient was treated with partial resection of the calcified plaques. Syringomyelia shunting was abandoned due to low volume. Post-operatively, the patient had improvement in their myelopathy though syrinx was still visualized on follow-up imaging. This report reviews the pathology, clinical and radiographic diagnosis, and treatment strategies for arachnoiditis ossificans.
- Published
- 2021
17. Abstract P5-16-13: First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex®
- Author
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L Bauer, C Ankel, A Faridi, J-U Blohmer, Stefan Paepke, B Krause-Bergmann, K Schnuppe, C Gerber-Schäfer, L Beier, C Neumann, Christine Mau, and HJ Strittmatter
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,Capsular contracture ,medicine.disease ,Group B ,Surgery ,Breast cancer ,Oncology ,Seroma ,medicine ,Implant ,business ,Complication ,Breast reconstruction - Abstract
Acellular dermal matrices (ADM) were used to cover the implant to reduce implant rotations and to improve esthetic results. Current retrospective data on complication rates are heterogeneous. Prospective data are rare. Primary objective was to evaluate the explantation rate. 11 German sites, with experience in breast reconstruction using ADM, have been selected for participation in this study. Patients were enrolled according to predefined in- and exclusion criteria into two cohorts: group A - primary reconstruction and group B - secondary reconstruction after capsular contracture. After documentation of baseline characteristics and surgical parameters, endpoints such as rate of seroma, red breast syndrome, infection and explantation were assed at 1 day, 7 days, 1 month, 3, 6 and 12 months after surgery. In addition, patient- and surgeon-satisfaction were recorded. Data of 83 patients were analyzed (A: 50, B: 33). In 29 patients Epiflex was used bilaterally, so that it was used 112-times in total. The average age of the patient was 45.1 years (A: 41.5; B: 50.3), the average BMI was 22.2 (A: 22.3; B: 22.1). In total, 17.0 % seromas (A: 19.4 %; B: 12.5 %), 10.7 % red breast syndrome (A: 9.7 %; B: 12.5 %), 4.5 % infections (A: 6.9 %; B: 0 %) and 5.4 % explantations (A: 6.9 %; B: 2.5 %) were observed. During the average observation period of 8 month, the satisfaction of the patients and surgeons was high at all measured time points. On a scale from (1 - very satisfied to 6 - not satisfied) the satisfaction of patients and surgeons was 2.3 (A: 2.3; B:1.9) and 2.0 (A: 2.2; B: 1.8) respectively. Our data show, that both patients and surgeons are generally satisfied with the outcome of breast reconstruction using ADM. Complication rates were adequate and commonly lower in secondary reconstructions. Citation Format: Blohmer J-U, Ankel C, Faridi A, Krause-Bergmann B, Neumann C, Schnuppe K, Beier L, Mau C, Strittmatter H-J, Gerber-Schäfer C, Bauer L, Paepke S. First results of the NOGGO-AWOGyn observational study: Skin and nipple sparing mastectomy and breast reconstruction with an implant and Epiflex® [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-16-13.
- Published
- 2019
18. Exosomes impact survival to radiation exposure in cell line models of nervous system cancer
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Oliver D. Mrowczynski, James R. Connor, Elias Rizk, Yuanjun Zhao, Russell Payne, Becky Slagle-Webb, Jeffrey M. Sundstrom, Yuka Imamura Kawasawa, A. B. Madhankumar, Brad E. Zacharia, and Christine Mau
- Subjects
0301 basic medicine ,glioblastoma ,Cancer ,exosomes ,Cell cycle ,Biology ,medicine.disease ,Exosome ,Microvesicles ,In vitro ,radiation ,resistance ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Mechanism of action ,Downregulation and upregulation ,glioma ,030220 oncology & carcinogenesis ,Cancer cell ,medicine ,Cancer research ,medicine.symptom ,Research Paper - Abstract
Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.
- Published
- 2018
19. Management of Diffuse Low-Grade Glioma: The Renaissance of Robust Evidence
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Fabio Y. Moraes, Jetan H. Badhiwala, Christine Mau, Farhad Pirouzmand, Karanbir Brar, Brad E. Zacharia, Laureen D. Hachem, and Alireza Mansouri
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Computer science ,diffuse low-grade glioma ,lcsh:RC254-282 ,Resection ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Medical physics ,neurosurgery ,Potential impact ,The Renaissance ,Foundation (evidence) ,artificial intelligence ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,machine learning ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Paradigm shift ,Perspective ,randomized controlled trials ,Observational study ,Low-Grade Glioma ,neuro-oncology - Abstract
The surgical management of diffuse low-grade gliomas (DLGGs) has undergone a paradigm shift toward striving for maximal safe resection when feasible. While extensive observational data supports this transition, unbiased evidence in the form of high quality randomized-controlled trials (RCTs) is lacking. Furthermore, despite a high volume of molecular, genetic, and imaging data, the field of neuro-oncology lacks personalized care algorithms for individuals with DLGGs based on a robust foundation of evidence. In this manuscript, we (1) discuss the logistical and philosophical challenges hindering the development of surgical RCTs for DLGGs, (2) highlight the potential impact of well-designed international prospective observational registries, (3) discuss ways in which cutting-edge computational techniques can be harnessed to generate maximal insight from high volumes of multi-faceted data, and (4) outline a comprehensive plan of action that will enable a multi-disciplinary approach to future DLGG management, integrating advances in clinical medicine, basic molecular research and large-scale data mining.
- Published
- 2020
20. External Ventricular Drain Migration Causing Parinaud’s Syndrome: A Case Report
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Ira M. Goldstein and Christine Mau
- Subjects
medicine.medical_specialty ,Subarachnoid hemorrhage ,Palsy ,business.industry ,General Engineering ,Parinaud's syndrome ,Neurosurgery ,Neurological exam ,Discharge home ,external ventricular drain ,030204 cardiovascular system & hematology ,medicine.disease ,neurosurgical procedures ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,dorsal midbrain syndrome ,medicine ,Acute hydrocephalus ,parinaud's syndrome ,business ,030217 neurology & neurosurgery ,Intracranial pressure ,External ventricular drain ,vertical gaze palsy - Abstract
Background External ventricular drains (EVD) are used for emergent management of acute hydrocephalus and for monitoring of intracranial pressure. Common complications of EVDs include malposition, infection, and hemorrhage. Here, the authors present a novel case of EVD migration causing Parinaud's syndrome. Case description A thirty-three-year-old female presented with witnessed seizure secondary to a left supraclinoid internal carotid artery aneurysm and trace subarachnoid hemorrhage. Two days after radiographic confirmation of an accurately placed EVD, she was found to have vertical gaze palsy (Parinaud's syndrome). Repeat CT head demonstrated inward migration of the EVD with left midbrain compression. After readjustment of the EVD, her Parinaud's syndrome improved each day until discharge home. Conclusions This is a novel clinical presentation of an EVD causing Parinaud's syndrome. There is only one other case report in the literature of this phenomenon. Although a practical solution to prevent this incident from occurring is unclear, vigilance for changes in neurological exam allowed for quick assessment and revision of the EVD and subsequent recovery in this patient.
- Published
- 2020
21. The Life and Death of Lord Nelson: The Leader, the Patient, the Legend
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Chirag D. Gandhi, Christine Mau, Victor Sabourin, Catherine E. Wassef, and Charles J. Prestigiacomo
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Male ,medicine.medical_specialty ,Battle ,Famous Persons ,media_common.quotation_subject ,medicine.medical_treatment ,Victory ,Charge (warfare) ,History, 18th Century ,Eye Injuries ,Medicine ,Craniocerebral Trauma ,Humans ,Naval Medicine ,Dominion ,media_common ,Arm Injuries ,business.industry ,General surgery ,Head injury ,Multitude ,Armed Conflicts ,medicine.disease ,Legend ,Amputation ,General Surgery ,Surgery ,Wounds, Gunshot ,Neurology (clinical) ,business - Abstract
Admiral Lord Horatio Nelson is perhaps the most renowned naval commander, who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries, including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury, and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.
- Published
- 2020
22. MON-262 A Case of the Suprasellar Atypical Teratoid Rhabdoid Tumor (ATRT) Presenting in an Adult Treated with Intrathecal Chemotherapy
- Author
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Christine Mau, Yahya H. Khormi, Lekhaj C Daggubati, Andrea Manni, Omar Oraibi, and Brad E. Zacharia
- Subjects
Pathology ,medicine.medical_specialty ,Neuroendocrinology and Pituitary ,business.industry ,Endocrinology, Diabetes and Metabolism ,Atypical teratoid rhabdoid tumor ,Medicine ,Case Reports in Unusual Pathologies in the Pituitary II ,Intrathecal chemotherapy ,business ,medicine.disease ,AcademicSubjects/MED00250 - Abstract
Background: Atypical teratoid rhabdoid tumors (ATRTs) are highly malignant tumors that usually present as a posterior fossa mass in children less than 3 years old. Only 38 cases have been reported in adults. They are also typically located in the supratentorial region. In none of the reported cases of suprasellar ATRT in the adult, intrathecal chemotherapy (via ommaya) has been used. Clinical case: A 70-year-old woman presented with a severe headache and magnetic resonance imaging (MRI) revealed a suprasellar mass measuring 2.9 x 2.1 x 3.0 cm. Shortly after her presentation, she developed an acute 3rd nerve palsy, and repeat MRI found dramatic interval growth. A transsphenoidal approach for biopsy/resection was attempted, but the lesion was not accessible via this corridor. She then underwent a right frontotemporal craniotomy and subsequently developed panhypopituitarism, including diabetes insipidus. Pathology revealed poorly differentiated malignant cells. Immunohistochemistry was positive for synaptophysin, Epithelial Membrane Antigen (EMA), Tumor protein p53, and negative for integrase interactor 1 (INI-1 antibody) with loss of expression in tumor nuclei with positive internal control in endothelial cells. These findings confirmed the diagnosis of ATRT. The Ki-67 index was 60% consistent with a highly proliferative tumor. One month later, she developed acute mental status change. Repeat computed tomography, and MRI showed recurrence of the tumor at the same location with new leptomeningeal enhancement involving the left facial nerve. Multimodal treatment was instituted, consisting of intraventricular/intrathecal chemotherapy with etoposide and topotecan plus fractionated external beam cranial irradiation (30 Gy in 10 fractions). She continued to deteriorate, and following consultation with her family, she was transferred to hospice care and died six months following her initial surgery. Conclusion: This is the first case of adult suprasellar ATRT that has been treated with intrathecal chemotherapy. There is no consensus on the best combination of chemotherapy, and often the St. Jude’s protocol used in the treatment of pediatric ATRT is used. In line with the biological behavior reported for this tumor in children and adults in different locations, the tumor was very aggressive, resulting in the patient’s death only after 6 months from the diagnosis despite aggressive surgical and medical treatment. Reference: 1. Athale, U. H., J. Duckworth, I. Odame, and R. Barr. 2009. Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J. Pediatr. Hematol. Oncol. 31:651-663. 2. Shonka N, Armstrong T (2011) Atypical teratoid/rhabdoid tumors in adults: A case report and treatment-focused review. J Clin Med Res 3: 85-92.
- Published
- 2020
23. Letter: COVID-19 Pandemic: Safety Precautions for Stereotactic Radiosurgery
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Leonard Tuanquin, Darrin V. Bann, Robert Saadi, Sandi Brettler, Vijay A. Patel, Huseyin Isildak, Brad E. Zacharia, Jeffrey Liaw, and Christine Mau
- Subjects
medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Neuros/18 ,business.industry ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,AcademicSubjects/MED00930 ,MEDLINE ,Clinical Neurology ,Radiosurgery ,Pandemic ,Correspondence ,medicine ,Surgery ,Neurology (clinical) ,Intensive care medicine ,business - Published
- 2020
24. Patient-Reported Outcomes and Aesthetic Results after Immediate Breast Reconstruction Using Human Acellular Dermal Matrices: Results of a Multicenter, Prospective, Observational NOGGO-AWOGyn Study
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Christine Mau, A Faridi, Stefan Paepke, C Ankel, Jens-Uwe Blohmer, Maren Keller, Barbara Krause-Bergmann, Hans Joachim Strittmatter, Lea Beier, and MM Karsten
- Subjects
medicine.medical_specialty ,business.industry ,Sexual functioning ,ddc ,Surgery ,Oncology ,Quality of life ,Cohort ,medicine ,Observational study ,Implant ,business ,Breast reconstruction ,Capsular fibrosis ,Prospective cohort study ,Research Article - Abstract
Background: With the increased use of acellular dermal matrices (ADMs) in implant-based breast reconstructions (IBBRs), the evaluation of patient-reported outcomes becomes more important. Methods: Patients who underwent an immediate human ADM-assisted, submuscular IBBR were included in this noninterventional, multicenter, prospective cohort study. Patients with primary reconstruction (cohort A) and patients with a revision surgery after capsular fibrosis (cohort B) were followed up for 12 months after surgery. Quality of life (EORTC BR-23) and patient and surgeon satisfaction scores (1 [“very satisfied”] to 6 [“not satisfied”]) with the outcome and the aesthetic result evaluated by 2 independent, external experts were assessed. Results: Eighty-four patients were enrolled in the study. The mean patient satisfaction score was 2.1 ± 0.8, with higher satisfaction in cohort B (p = 0.041). The score did not change significantly during the follow-up (p = 0.479). The mean satisfaction score of the surgeons was 2.0 ± 0.7; it was also higher in cohort B (p = 0.016) and showed no changes over time (p = 0.473). The mean aesthetic result was 2.2 ± 0.7. 92.9% of the patients completed at least 1 quality of life questionnaire. Body image and sexual functioning increased during follow-up. One year after surgery, the mean scores were 77.2 ± 22.5 and 44.7 ± 27.3, respectively. Conclusion: The level of satisfaction among patients and surgeons and the score of the aesthetic result were constantly high among patients after ADM-assisted IBBR. Higher satisfaction scores could be observed after revision surgery caused by capsular fibrosis (cohort B) compared to primary reconstruction (cohort A). Quality of life increased during the first year after surgery.
- Published
- 2020
25. Patient reported outcome and cosmetic evaluation following implant-based breast-reconstruction with a titanized polypropylene mesh (TiLOOP® Bra): A prospective clinical study in 269 patients
- Author
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Hans-Joachim Strittmatter, A Faridi, Anette Meiré, Kristin Baumann, Claudia Gerber-Schäfer, Elke Nolte, Ralf Ohlinger, Stefan Paepke, Jens-Uwe Blohmer, Marc Thill, Sabrina Tofall, and Christine Mau
- Subjects
Adult ,medicine.medical_specialty ,Esthetics ,Breast Implants ,Mammaplasty ,Breast Neoplasms ,030230 surgery ,Polypropylenes ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Patient Reported Outcome Measures ,Prospective Studies ,skin and connective tissue diseases ,Adverse effect ,Aged ,Neoplasm Staging ,business.industry ,Cancer ,General Medicine ,Middle Aged ,Surgical Mesh ,medicine.disease ,ddc ,Surgery ,Polypropylene mesh ,Surgical mesh ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Patient-reported outcome ,Female ,Implant ,Lymph Nodes ,Breast reconstruction ,business ,Psychosocial - Abstract
Implant-based or expander-supported breast reconstruction is an established surgical method after mastectomies due to cancer or to prophylactic reasons. Patient reported outcome (PRO) and cosmetic outcome after breast reconstruction with a synthetic surgical mesh was investigated in a prospective, single-arm, multi-center study.Primary or secondary implant-based breast reconstruction with support of TiLOOP® Bra was performed in 269 patients during the PRO-BRA study. PRO 12 months after breast reconstruction was evaluated using Breast-Q questionnaire. Cosmetic outcome was evaluated by two independent experts by means of pictures taken preoperatively and at the follow-up visits.Breast-Q and 12 months FU were completed by 210 women. Patients without adverse event had a significantly higher Breast-Q score for "sexual well-being" (p = 0.001); "psychosocial well-being" was negatively influenced by prior therapies (p 0.01), and older patients had significantly lower scores at 12 months FU compared to pre-OP for "satisfaction with breasts" (p 0.01) while the opposite was true for younger patients. Unilateral surgery resulted in reduced "satisfaction with breast" at 12 months FU (p 0.01). Radiotherapy negatively influenced "satisfaction with breast", "sexual well-being" and "physical well-being chest". The cosmetic evaluation showed a significant difference (p 0.001) in the evaluation by the patients and experts with the patients' assessment being worse compared to experts' assessment.Our study showed that two years after implant-based breast reconstruction with support of TiLOOP® Bra PRO is influenced by different factors. This information can be used to improve the decision-making process for women who chose implant-based breast reconstruction.
- Published
- 2020
26. Human Acellular Dermal Matrix (Epiflex®) in Immediate Implant-Based Breast Reconstruction after Skin- and Nipple-Sparing Mastectomy and Treatment of Capsular Fibrosis: Results of a Multicenter, Prospective, Observational NOGGO-AWOGyn Study
- Author
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Christine Mau, Stefan Paepke, Lea Beier, A Faridi, Corina Neumann, Lelia Bauer, Sherko Kümmel, Hans Joachim Strittmatter, Claudia Gerber-Schäfer, MM Karsten, Jens-Uwe Blohmer, and Maren Keller
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Postoperative complication ,medicine.disease ,Surgery ,Radiation therapy ,Oncology ,Seroma ,Cohort ,Medicine ,Implant ,business ,Prospective cohort study ,Breast reconstruction ,Complication ,Research Article - Abstract
Background: Over the last decades, the number of acellular dermal matrix (ADM)-assisted implant-based breast reconstructions (IBBR) has substantially increased. However, there is still a lack of prospective data on complication rates. Methods: We performed a non-interventional, multicenter, prospective cohort study to evaluate complication rates of a human ADM in patients undergoing an IBBR after skin- and nipple-sparing mastectomies. Patients with primary reconstruction (cohort A) and patients undergoing a secondary reconstruction after capsular fibrosis (cohort B) using the human ADM Epiflex® (DIZG gGmbH, Berlin, Germany) were enrolled in this study. Patients were followed-up for 12 months after surgery. Results: Eighty-four eligible patients were included in this study of whom 28 women underwent a bilateral breast reconstruction, leading to 112 human ADM-assisted reconstructions in total (cohort A: 73, cohort B: 39). In 33.0% of the reconstructed breasts at least one of the complications of primary interest occurred, including implant loss 7.1%, seroma 15.2%; infection 5.4%, rash 8.0%, and Baker grade III/IV capsular fibrosis 2.7%, with no statistically significant differences between the cohorts. Previous radiation therapy was significantly associated with occurrence of any postoperative complication (OR 20.41; p value 0.027). Conclusion: The rates of most complications were comparable to the rates reported for other ADMs with relatively low rates of capsular fibrosis and infections. The rate of seroma was increased in our study. Prior radiation therapy increased the risk of any postoperative complications. Therefore, the use of ADM in these patients should be considered carefully.
- Published
- 2020
27. Superior semicircular canal dehiscence: Diagnosis and management
- Author
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Naveed Kamal, James K. Liu, Renuka K. Reddy, Saiaditya Badeti, Robert W. Jyung, Christine Mau, and Yu Lan Mary Ying
- Subjects
medicine.medical_specialty ,Vestibular evoked myogenic potential ,Labyrinth Diseases ,Dehiscence ,03 medical and health sciences ,0302 clinical medicine ,Audiometry ,Physiology (medical) ,Temporal bone ,otorhinolaryngologic diseases ,medicine ,Humans ,030223 otorhinolaryngology ,medicine.diagnostic_test ,Semicircular canal ,business.industry ,Temporal Bone ,General Medicine ,Magnetic Resonance Imaging ,Vestibular Evoked Myogenic Potentials ,Semicircular Canals ,medicine.anatomical_structure ,Neurology ,Otorhinolaryngology ,Otologic Surgical Procedures ,Surgery ,sense organs ,Neurology (clinical) ,Radiology ,Neurosurgery ,Tomography, X-Ray Computed ,business ,030217 neurology & neurosurgery - Abstract
The authors provide an update on the clinical manifestations, diagnosis and various approaches to the treatment of superior semicircular canal dehiscence (SSCD). SSCD is a rare condition where the bone overlying the superior semicircular canal thins or dehisces causing characteristic clinical findings. Since this was first reported in 1998 by Minor and colleagues, there has been much advancement made in terms of diagnosis and treatment. Signs and symptoms include a wide variation of both vestibular and auditory manifestations. Diagnosis made solely on clinical signs is difficult due to how varied the presentations can be and the overlap with other otologic pathologies. High-resolution CT temporal scans have been the standard in confirming superior semicircular canal dehiscence, however, MRI FIESTA scans have recently been used to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential (VEMP) testing are useful screening tools. Currently, the middle fossa approach is the most common and standard surgical approach to repair SSCD. The transmastoid, endoscopic and transcanal or endaural approaches have also been recently utilized. Presently, there is no consensus as to the best approach, material or technique for repair of SSCD. As we learn more, newer and less invasive approaches and techniques are being used to treat SSCD. We present a comprehensive review of SSCD, including clinical symptoms and presentation, histopathology, diagnosis, treatment strategies and outcomes of intervention.
- Published
- 2018
28. Equivalent Efficacy and Safety of Radiosurgery for Cystic and Solid Vestibular Schwannomas: A Systematic Review
- Author
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Elie Massaad, Brad E. Zacharia, Varun Padmanaban, Caroline Chung, Christine Mau, Jacalynn Goetz, Fabio Y. Moraes, Alireza Mansouri, Derek S. Tsang, and Nima Hamidi
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Acoustic neuroma ,Neuroma, Acoustic ,Radiosurgery ,Tumor control ,medicine.disease ,Confidence interval ,03 medical and health sciences ,Treatment Outcome ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Relative risk ,Vestibular Schwannomas ,medicine ,Humans ,Surgery ,Cyst ,Neurology (clinical) ,Radiology ,business ,Adverse effect ,030217 neurology & neurosurgery - Abstract
Background Cystic vestibular schwannomas (VS) are associated with unpredictable growth behavior and potentially worse surgical outcomes compared with their solid counterparts. Growth control and potential adverse effects of radiosurgery for cystic VS have created concerns surrounding this modality. We sought to compare the treatment efficacy and safety profile of radiosurgery between cystic and solid VS through a systematic review. Methods PubMed, EMBASE, Web of Science, and Cochrane were searched for related terms and studies reporting radiosurgical outcomes of cystic and solid VS. A meta-analysis was performed to compare the rates of tumor control. Random-effect models with generic inverse variance method was used to calculate overall pooled estimates. Study quality was assessed with the Newcastle Ottawa Criteria. Results In total, 2989 studies were retrieved, and 6 including 1358 VS (79.89% solid; 20.11% cystic, median follow-up range 31.8–150 months) were selected. The median maximal dose was 25 Gy (range, 13–36 Gy) and the median marginal tumor dose was 12 Gy (10–18 Gy). There was no difference between cystic and solid VS (risk ratio, 1.02; 95% confidence interval 0.94–1.10; P = 0.69; I2 = 78%). Transient enlargement of cystic tumors may be associated with trigeminal or facial neuropathy. Conclusions The evidence collected by this study suggests that radiosurgery for cystic VS exhibits effective tumor control probabilities similar to solid VS. Consensus definitions and standard criteria are needed in the future to better understand the patterns of tumor growth and response to treatment following radiosurgery for cystic VS, as well as long-term neurological and functional outcomes.
- Published
- 2021
29. Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain injury patients: implementation and evaluation of a new protocol
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Chirag G. Gordhan, Charles J. Prestigiacomo, Seema P. Anandalwar, Ziad C. Sifri, Christine Mau, Ahmed Meleis, and Neil Majmundar
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Adult ,Male ,medicine.medical_specialty ,Traumatic brain injury ,Poison control ,Unnecessary Procedures ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Skull fracture ,medicine ,Humans ,Brain Concussion ,Retrospective Studies ,business.industry ,Trauma center ,Head injury ,Glasgow Coma Scale ,030208 emergency & critical care medicine ,General Medicine ,Emergency department ,medicine.disease ,Surgery ,Blunt trauma ,Female ,Tomography, X-Ray Computed ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVE The utility of routine repeat head CT (HCT) scans in the management of minimal head injury (MHI) patients with an intracranial hemorrhage (ICH) has been questioned in multiple studies. All these studies analyzed this by obtaining a repeat HCT study, and none examined the effects of eliminating these routine HCT studies in neurologically intact patients. The authors' institution implemented a new “Neurologic Observation without Repeat HCT” (NORH) protocol with no repeat HCT scanning for patients admitted for MHI and ICH whose neurological status was maintained or improved to a Glasgow Coma Scale score of 15 at 24 hours after admission. This purpose of this study was to assess the outcomes and safety of this novel protocol. METHODS Records of patients who sustained blunt trauma MHI and an ICH and/or skull fracture on initial HCT between January 1, 2009, and December 31, 2012, were retrieved from the trauma registry of a Level I trauma center. The authors analyzed 95 patients in whom the NORH protocol was followed. Outcome measures included death, emergency department readmission, neurosurgical intervention, delayed repeat HCT, and length of stay. RESULTS The NORH protocol was followed for 95 patients; 83% of the patients were male, the average age was 38 ± 16.0 years old, and the most common cause of trauma was assault (35%). Of the 95 patients in whom the NORH protocol was followed, 8 (8%) had a delayed repeat HCT study (> 24 hours) after admission, but none resulted in neurosurgical intervention because of progression of ICH. The average length of stay was 4 ± 7.2 days. None of the patients were readmitted to the hospital. CONCLUSIONS Implementation of the NORH protocol (eliminating routine follow-up HCT) resulted in very low rates of delayed neurological deterioration, no late neurosurgical interventions resulting from ICH progression, very few emergency department revisits, and no readmissions. For a select group of MHI patients with ICH, the NORH protocol is safe and effective, and can reduce radiation exposure and costs.
- Published
- 2016
30. Patient Reported Outcome and cosmetic evaluation following implant-based breast-reconstruction with a titanized polypropylene mesh: A prospective clinical study in 269 patients
- Author
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HJ Strittmatter, Christine Mau, E Klein, A Faridi, C. Baumann, J-U Blohmer, Stefan Paepke, S. Tofall, C Gerber-Schäfer, A Meiré, R. Ohlinger, Marc Thill, and E Nolte
- Subjects
Polypropylene mesh ,Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Prospective clinical study ,Medicine ,Patient-reported outcome ,Implant ,business ,Breast reconstruction ,Surgery - Published
- 2020
31. Patienten- und Operateurzufriedenheit in der Brustrekonstruktion mit Epiflex® – NOGGO-AWOGyn-Intergroupstudie
- Author
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C Neumann, Stefan Paepke, B Krause-Bergmann, A Faridi, Christine Mau, HJ Strittmatter, C Ankel, L Bauer, L Beier, C Gerber-Schäfer, K Schnuppe, and J-U Blohmer
- Published
- 2018
32. Neuroleukemiosis: Diagnosis and management
- Author
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Christine Mau, Elias Rizk, Michael George Zaki Ghali, Jozef Malysz, Charles S. Specht, and Michael Styler
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Male ,medicine.medical_specialty ,Nerve root ,03 medical and health sciences ,Myelogenous ,Young Adult ,0302 clinical medicine ,Immunophenotyping ,Biopsy ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Disease Management ,Peripheral Nervous System Diseases ,General Medicine ,medicine.disease ,Leukemia ,Leukemia, Myeloid, Acute ,Peripheral neuropathy ,030220 oncology & carcinogenesis ,Surgery ,Histopathology ,Neurology (clinical) ,Radiology ,business ,030217 neurology & neurosurgery ,Lumbosacral joint - Abstract
An exceedingly rare manifestation of leukemia, termed neuroleukemiosis, involves peripheral nerve infiltration by leukemic cells. Patients with neuroleukemiosis typically present with a peripheral neuropathy and/or chloromatous masses. The diagnosis is supported by, and established with, electrophysiologic testing, imaging, histopathology, and immunophenotyping. We present the case of 21 year old male with multiply relapsed M4 type of acute myelogenous leukemia (AML) who presented with extremity pain and was subsequently found to have multiple cervical, thoracic, and lumbosacral nerve root masses. A diagnosis of neuroleukemiosis was established via CT-guided biopsy and immunophenotyping. The patient's neuroleukemiosis responded well to chemotherapy, donor lymphocyte infusions, and spinal irradiation. The literature is reviewed regarding this interesting and rare clinical condition.
- Published
- 2018
33. Percutaneous Radiofrequency Ablation for the Treatment of Peripheral Nerve Sheath Tumors: A Case Report and Review of the Literature
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Oliver D. Mrowczynski, Kimberly Harbaugh, Nabeel Sarwani, Dan T Nguyen, Christine Mau, and Elias Rizk
- Subjects
medicine.medical_specialty ,Percutaneous ,Radiofrequency ablation ,Neurosurgery ,review ,Schwannoma ,peripheral nerve tumors ,law.invention ,neurofibroma ,03 medical and health sciences ,0302 clinical medicine ,radiofrequency ,law ,medicine ,Peripheral Nerve Sheath Tumors ,Neurofibroma ,Neurofibromatosis ,Schwannomatosis ,schwannoma ,business.industry ,General Engineering ,Multiple Neurofibromas ,medicine.disease ,030220 oncology & carcinogenesis ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
Peripheral nerve sheath tumors (PNSTs) may arise sporadically or in the presence of genetic disorders, including neurofibromatosis (NF) types 1 and 2, schwannomatosis, and in patients with large genetic deletions involving the CDKN2A gene. Surgical resection is the treatment of choice for symptomatic PNSTs and offers patients a potential cure; however, pre-existing conditions or tumor location may limit a patient's surgical options. Radiofrequency ablation (RFA) may provide an alternative therapeutic strategy for the treatment of selected PNSTs that are not amenable to surgical resection. Here, we present a case report of a 49-year-old patient with multiple neurofibromas who underwent RFA treatment of two symptomatic retroperitoneal neurofibromas and review previously reported cases of percutaneous treatment of PNSTs.
- Published
- 2018
34. TMOD-28. INTERLEUKIN-13 TARGETED PSEUDOMONAS TOXIN TREATMENT OF MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
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Alexandre J. Bourcier, James D. Connor, Oliver D. Mrowczynski, Kimberly Harbaugh, Becky Slagle-Webb, Christine Mau, A.B. Madhankumar, Russell Payne, and Elias Rizk
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,biology ,Toxin ,business.industry ,Pseudomonas ,biology.organism_classification ,medicine.disease_cause ,Abstracts ,Text mining ,Oncology ,Interleukin 13 ,Peripheral Nerve Sheath Tumors ,medicine ,Neurology (clinical) ,business - Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerves. A target of MPNSTs is the receptor for interleukin-13 (IL-13R). IL-13R has an α1 and α2 subtype, and activation of α1 leads to caspase-3 mediated apoptosis. MPNSTs have increased expression of the α2 subtype, IL-13Rα2. IL-13Rα2 is an oncogene that acts as a decoy receptor which has a higher affinity for IL-13, allowing cancer to evade death by binding and sequestering all of the IL-13 thus inhibiting α1 activation. Decreased α1 activation enhances tumor cell survival and augments the high potential for metastasis. The subsequent increased tumorigenicity is then followed by the devastating prognosis with five year survival ranging from a dismal 15-60%. MPNSTs are currently treated with surgical resection, sometimes requiring complete limb amputation, as well as chemoradiation, all of which demonstrate limited effectiveness, and highlight the necessity for novel therapies. The goal of this study was to demonstrate the effectiveness of intratumoral Interleukin-13 targeted pseudomonas exotoxin (IL13E13K-PE4E) for MPNST treatment. The upregulated IL-13Rα2 on MPNSTs provides a unique opportunity for utilizing IL13E13K-PE4E to precisely target MPNSTs and cause tumor cell death. We demonstrate that IL13E13K-PE4E treatment led to a 4-fold decrease in tumor progression in vivo. IHC analysis showed increased necrosis, decreased Ki67, and increased cleaved caspase-3, corroborating the in vivo findings. The specific targeting of IL-13Rα2 also leads to a decreased side effect profile due to minimal IL-13Rα2 expression in normal tissues. The current MPNST treatment paradigm is composed of 3-prongs: surgery, chemotherapy, and radiation, all of which have been demonstrated to be unsatisfactory. This study lays the groundwork for the change of this paradigm and subsequently optimal patient outcomes by the addition of a 4th prong, intratumoral treatment with IL13E13K-PE4E.
- Published
- 2017
35. Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study
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Bernd Gerber, Diether Lambrechts, Mahdi Rezai, Matthieu Moisse, Christian Schem, Jens Huober, Volkmar Müller, Georg Kunz, Claus Hanusch, Serban-Dan Costa, Gilian Peuteman, K. Schwedler, Richard M. Weinshilboum, Brigitte Rack, Jens Uwe Blohmer, Peter A. Fasching, Thomas Van Brussel, Valentina Nekljudova, K Kittel, Michael Untch, Matthias W. Beckmann, Christine Mau, Lothar Häberle, Gunter von Minckwitz, Cornelia Liedtke, Jörn Hilfrich, Holger Eidtmann, Arif B. Ekici, Matthias Rübner, Alexander Hein, Liewei Wang, Hans Tesch, Sibylle Loibl, and Tanja Fehm
- Subjects
Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Pathology ,Bevacizumab ,business.industry ,medicine.medical_treatment ,Single-nucleotide polymorphism ,Odds ratio ,medicine.disease ,Breast cancer ,Internal medicine ,Genotype ,medicine ,SNP ,Biomarker (medicine) ,business ,medicine.drug - Abstract
Studies assessing the effect of bevacizumab (BEV) on breast cancer (BC) outcome have shown different effects on progression-free and overall survival, suggesting that a subgroup of patients may benefit from this treatment. Unfortunately, no biomarkers exist to identify these patients. Here, we investigate whether single nucleotide polymorphisms (SNPs) in VEGF pathway genes correlate with pathological complete response (pCR) in the neoadjuvant GeparQuinto trial. HER2-negative patients were randomized into treatment arms receiving either BEV combined with standard chemotherapy or chemotherapy alone. In a pre-planned biomarker study, DNA was collected from 729 and 724 patients, respectively from both treatment arms, and genotyped for 125 SNPs. Logistic regression assessed interaction between individual SNPs and both treatment arms to predict pCR. Five SNPs may be associated with a better response to BEV, but none of them remained significant after correction for multiple testing. The two SNPs most strongly associated, rs833058 and rs699947, were located upstream of the VEGF-A promoter. Odds ratios for the homozygous common, heterozygous and homozygous rare rs833058 genotypes were 2.36 (95% CI, 1.49-3.75), 1.20 (95% CI, 0.88-1.64) and 0.61 (95% CI, 0.34-1.12). Notably, some SNPs in VEGF-A exhibited a more pronounced effect in the triple-negative subgroup. Several SNPs in VEGF-A may be associated with improved pCR when receiving BEV in the neoadjuvant setting. Although none of the observed effects survived correction for multiple testing, our observations are consistent with previous studies on BEV efficacy in BC. Further research is warranted to clarify the predictive value of these markers.
- Published
- 2015
36. Nitric Oxide Synthase 1 Adaptor Protein, a Protein Implicated in Schizophrenia, Controls Radial Migration of Cortical Neurons
- Author
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Munjin Kwon, Bonnie L. Firestein, Damien Carrel, Kristina Hernandez, Christine Mau, Meera P. Trivedi, and Linda M. Brzustowicz
- Subjects
Male ,Phosphotyrosine binding ,Green Fluorescent Proteins ,PDZ Domains ,Neocortex ,Biology ,Transfection ,Green fluorescent protein ,Neural Stem Cells ,Cell Movement ,Pregnancy ,NOS1AP ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Biological Psychiatry ,Adaptor Proteins, Signal Transducing ,Gene Expression Regulation, Developmental ,Signal transducing adaptor protein ,Embryo, Mammalian ,Neural stem cell ,Rats ,3. Good health ,Cell biology ,Luminescent Proteins ,medicine.anatomical_structure ,Animals, Newborn ,COS Cells ,Mutation ,Female ,Neuron ,Rats, Transgenic ,Neuroscience - Abstract
Background Where a neuron is positioned in the brain during development determines neuronal circuitry and information processing needed for normal brain function. When aberrations in this process occur, cognitive disorders may result. Patients diagnosed with schizophrenia have been reported to show altered neuronal connectivity and heterotopias. To elucidate pathways by which this process occurs and become aberrant, we have chosen to study the long isoform of nitric oxide synthase 1 adaptor protein (NOS1AP), a protein encoded by a susceptibility gene for schizophrenia. Methods To determine whether NOS1AP plays a role in cortical patterning, we knocked down or co-overexpressed NOS1AP and a green fluorescent protein or red fluorescent protein (TagRFP) reporter in neuronal progenitor cells of the embryonic rat neocortex using in utero electroporation. We analyzed sections of cortex (ventricular zone, intermediate zone, and cortical plate [CP]) containing green fluorescent protein or red fluorescent protein TagRFP positive cells and counted the percentage of positive cells that migrated to each region from at least three rats for each condition. Results NOS1AP overexpression disrupts neuronal migration, resulting in increased cells in intermediate zone and less cells in CP, and decreases dendritogenesis. Knockdown results in increased migration, with more cells reaching the CP. The phosphotyrosine binding region, but not the PDZ-binding motif, is necessary for NOS1AP function. Amino acids 181 to 307, which are sufficient for NOS1AP-mediated decreases in dendrite number, have no effect on migration. Conclusions Our studies show for the first time a critical role for the schizophrenia-associated gene NOS1AP in cortical patterning, which may contribute to underlying pathophysiology seen in schizophrenia.
- Published
- 2015
37. MLN8237 treatment in an orthoxenograft murine model for malignant peripheral nerve sheath tumors
- Author
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Kimberly Harbaugh, Oliver D. Mrowczynski, Christine Mau, Alexandre J. Bourcier, James R. Connor, Becky Slagle-Webb, Russell Payne, Dawit Aregawi, A. B. Madhankumar, Elias Rizk, and Sang Y. Lee
- Subjects
Oncology ,0303 health sciences ,medicine.medical_specialty ,Ifosfamide ,business.industry ,Malignant peripheral nerve sheath tumor ,General Medicine ,medicine.disease ,Metastasis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Aurora kinase ,chemistry ,In vivo ,030220 oncology & carcinogenesis ,Internal medicine ,Alisertib ,medicine ,Doxorubicin ,business ,Survival analysis ,030304 developmental biology ,medicine.drug - Abstract
OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas arising from peripheral nerves. MPNSTs have increased expression of the oncogene aurora kinase A, leading to enhanced cellular proliferation. This makes them extremely aggressive with high potential for metastasis and a devastating prognosis; 5-year survival estimates range from a dismal 15% to 60%. MPNSTs are currently treated with resection (sometimes requiring limb amputation) in combination with chemoradiation, both of which demonstrate limited effectiveness. The authors present the results of immunohistochemical, in vitro, and in vivo analyses of MLN8237 for the treatment of MPNSTs in an orthoxenograft murine model.METHODSImmunohistochemistry was performed on tumor sections to confirm the increased expression of aurora kinase A. Cytotoxicity analysis was then performed on an MPNST cell line (STS26T) to assess the efficacy of MLN8237 in vitro. A murine orthoxenograft MPNST model transfected to express luciferase was then developed to assess the efficacy of aurora kinase A inhibition in the treatment of MPNSTs in vivo. Mice with confirmed tumor on in vivo imaging were divided into 3 groups: 1) controls, 2) mice treated with MLN8237, and 3) mice treated with doxorubicin/ifosfamide. Treatment was carried out for 32 days, with imaging performed at weekly intervals until postinjection day 42. Average bioluminescence among groups was compared at weekly intervals using 1-way ANOVA. A survival analysis was performed using Kaplan-Meier curves.RESULTSImmunohistochemical analysis showed robust expression of aurora kinase A in tumor cells. Cytotoxicity analysis revealed STS26T susceptibility to MLN8237 in vitro. The group receiving treatment with MLN8237 showed a statistically significant difference in tumor size compared with the control group starting at postinjection day 21 and persisting until the end of the study. The MLN8237 group also showed decreased tumor size compared with the doxorubicin/ifosfamide group at the conclusion of the study (p = 0.036). Survival analysis revealed a significantly increased median survival in the MLN8237 group (83 days) compared with both the control (64 days) and doxorubicin/ifosfamide (67 days) groups. A hazard ratio comparing the 2 treatment groups showed a decreased hazard rate in the MLN8237 group compared with the doxorubicin/ifosfamide group (HR 2.945; p = 0.0134).CONCLUSIONSThe results of this study demonstrate that MLN8237 is superior to combination treatment with doxorubicin/ifosfamide in a preclinical orthoxenograft murine model. These data have major implications for the future of MPNST research by providing a robust murine model as well as providing evidence that MLN8237 may be an effective treatment for MPNSTs.
- Published
- 2017
38. Head injury in heroes of the Civil War and its lasting influence
- Author
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Charles J. Prestigiacomo, Chirag D. Gandhi, Victor M. Sabourin, Ryan Holland, and Christine Mau
- Subjects
Gerontology ,Social Work ,Medical Indigency ,Population ,Poison control ,030230 surgery ,Suicide prevention ,03 medical and health sciences ,0302 clinical medicine ,History of the United States ,Injury prevention ,Economic history ,Medicine ,Craniocerebral Trauma ,Humans ,education ,education.field_of_study ,Social work ,business.industry ,History, 19th Century ,General Medicine ,History, 20th Century ,United States ,Black or African American ,Military personnel ,Spanish Civil War ,Military Personnel ,American Civil War ,Surgery ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
The Civil War era was an age-defining period in the history of the United States of America, the effects of which are still seen in the nation today. In this era, the issue of head injury pervaded society. From the president of the United States, Abraham Lincoln, to the officers and soldiers of the Union and Confederate armies, and to the population at large, head injury and its ramifications gripped the nation. This article focuses on 3 individuals: Major General John Sedgwick, First Lieutenant Alonzo Cushing, and Harriet Tubman, as examples of the impact that head injury had during this era. These 3 individuals were chosen for this article because of their lasting legacies, contributions to society, and interesting connections to one another.
- Published
- 2016
39. Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab – a translational project in the neoadjuvant GeparQuinto trial
- Author
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S. Loibl, Joyce Bischoff, Thomas Karn, Yasmin Issa-Nummer, Christian Schem, I. Meinhold-Heerlein, Maik Hauschild, Brigitte Rack, Volkmar Müller, C. zu Eulenburg, Michael Untch, F Khandan, H. Eidtmann, Peter A. Fasching, Sabine Schmatloch, J Huober, Christine Mau, Cornelia Liedtke, G. von Minckwitz, Tanja Fehm, and Isabell Witzel
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Antineoplastic Agents ,Breast Neoplasms ,Enzyme-Linked Immunosorbent Assay ,Antibodies, Monoclonal, Humanized ,Lapatinib ,Drug Administration Schedule ,law.invention ,Translational Research, Biomedical ,breast cancer ,Randomized controlled trial ,Predictive Value of Tests ,Trastuzumab ,law ,HER2 ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,neoadjuvant therapy ,lapatinib ,skin and connective tissue diseases ,Neoadjuvant therapy ,Aged ,Chemotherapy ,business.industry ,Middle Aged ,Clinical trial ,Treatment Outcome ,Endocrinology ,Receptors, Estrogen ,Predictive value of tests ,Multivariate Analysis ,Cohort ,Quinazolines ,Clinical Study ,Female ,business ,serum ,medicine.drug - Abstract
Background: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear. Methods: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points. Results: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml−1). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02–3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3–110, P=0.031). Conclusion: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml−1) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.
- Published
- 2012
40. 30 Jahre Österreichische Gesellschaft für Senologie
- Author
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Tony Ng, Ulrike Freitag, Goran Azanjac, Martin Radespiel-Tröger, Anton Scharl, Volkan Kaynarog lu, Christoph Thomssen, Marion Kiechle, Sybille Loibl, Gabriele Klühs, Viktoria Aivazova-Fuchs, Ulrike Braisch, Karla Geiss, Dragan Čanović, Christine Mau, Philip Hepp, Julia Jückstock, Alexandra Schönherr, Derya Karakoc, Wolfgang Janni, W. Simon, Ali Konan, Fabrice Andre, Martin Meyer, Jasmina Nedovic, Michael Untch, Sherene Loi, Carmen Criscitiello, Ulrich Andergassen, Giuseppe Curigliano, Sheeba Irshad, İsmail Doğan, A Wischnik, Cristina Pirvulescu, Sedat Kiraz, Andrew Tutt, Klaus Friese, Ali Akdogan, Katherine Lawler, Brigitte Rack, Doris Augustin, Milan Knezevic, Nadia Harbeck, Katja Annecke, Barbara Fleige, J. Salmen, Demirali Onat, Umut Kalyoncu, Srdjan Ninkovic, Yusuf Alper Kilic, Davide Serrano, Holger Schultz, Slobodanka Mitrovic, Matteo Lazzeroni, Peter Dubsky, John Stagg, Thomas Zwingers, Nadja Harbeck, Dragce Radovanovic, Annette Isbruch, Heike Renner-Lützkendorf, Anita Grigoriadis, Nikolaos S. Salemis, Svjetlana Mohrmann, and Antje Sperfeld
- Subjects
Oncology ,business.industry ,Medicine ,Surgery ,business ,Humanities - Published
- 2012
41. Breast Cancer during Pregnancy: An Interdisciplinary Approach in Our Institution
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Cristina Pirvulescu, Gabriele Klühs, Barbara Fleige, Sybille Loibl, Michael Untch, Ulrike Freitag, Annette Isbruch, Antje Sperfeld, Holger Schultz, Heike Renner-Lützkendorf, and Christine Mau
- Subjects
Oncology ,medicine.medical_specialty ,Pregnancy ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Surgery ,Radiation therapy ,Breast cancer ,Internal medicine ,medicine ,Case Report • Kasuistik ,skin and connective tissue diseases ,business ,Tamoxifen ,Neoadjuvant therapy ,medicine.drug ,Epirubicin - Abstract
Summary Background: Breast cancer is the most common cancer diagnosed during pregnancy. Case Report: We report on a case of a 26-year-old woman who was diagnosed with right-sided breast cancer in her 15th week of gestation. We discussed possible treatment scenarios and the patient opted for neoadjuvant therapy with taxanes and anthracyclines during pregnancy, followed by delivery and then followed by surgery, antibody therapy, and radiotherapy. The patient received neoadjuvant chemotherapy with paclitaxel 80 mg/m2 weekly for 12 cycles, followed by 4 cycles of epirubicin and cyclophosphamide (90/600 mg/m 2 ) every 3 weeks. Complete clinical response was seen after preoperative chemotherapy. After delivery of a healthy child at 40 weeks of gestation, she received breast-conserving surgery and axillary dissection. Anti-HER2 antibody treatment with trastuzumab was started concomitantly with adjuvant radiotherapy. Endocrine treatment with a gonadotropin-releasing hormone (GnRH) analog and tamoxifen for 5 years was planned to be started after radiotherapy. Conclusion: Treatment of breast cancer during pregnancy requires an interdisciplinary approach and careful consideration of the patient’s stage of disease, the gestational age, and the preferences of the patient and her family.
- Published
- 2012
42. Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study
- Author
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Alexander, Hein, Diether, Lambrechts, Gunter, von Minckwitz, Lothar, Häberle, Holger, Eidtmann, Hans, Tesch, Michael, Untch, Jörn, Hilfrich, Christian, Schem, Mahdi, Rezai, Bernd, Gerber, Serban, Dan Costa, Jens-Uwe, Blohmer, Kathrin, Schwedler, Kornelia, Kittel, Tanja, Fehm, Georg, Kunz, Matthias W, Beckmann, Arif B, Ekici, Claus, Hanusch, Jens, Huober, Cornelia, Liedtke, Christine, Mau, Matthieu, Moisse, Volkmar, Müller, Valentina, Nekljudova, Gilian, Peuteman, Brigitte, Rack, Matthias, Rübner, Thomas, Van Brussel, Liewei, Wang, Richard M, Weinshilboum, Sibylle, Loibl, and Peter A, Fasching
- Subjects
Adult ,Vascular Endothelial Growth Factor A ,Genotype ,Neovascularization, Pathologic ,Angiogenesis Inhibitors ,Breast Neoplasms ,Middle Aged ,Polymorphism, Single Nucleotide ,Neoadjuvant Therapy ,Bevacizumab ,Treatment Outcome ,Chemotherapy, Adjuvant ,Humans ,Female ,Genetic Association Studies - Abstract
Studies assessing the effect of bevacizumab (BEV) on breast cancer (BC) outcome have shown different effects on progression-free and overall survival, suggesting that a subgroup of patients may benefit from this treatment. Unfortunately, no biomarkers exist to identify these patients. Here, we investigate whether single nucleotide polymorphisms (SNPs) in VEGF pathway genes correlate with pathological complete response (pCR) in the neoadjuvant GeparQuinto trial. HER2-negative patients were randomized into treatment arms receiving either BEV combined with standard chemotherapy or chemotherapy alone. In a pre-planned biomarker study, DNA was collected from 729 and 724 patients, respectively from both treatment arms, and genotyped for 125 SNPs. Logistic regression assessed interaction between individual SNPs and both treatment arms to predict pCR. Five SNPs may be associated with a better response to BEV, but none of them remained significant after correction for multiple testing. The two SNPs most strongly associated, rs833058 and rs699947, were located upstream of the VEGF-A promoter. Odds ratios for the homozygous common, heterozygous and homozygous rare rs833058 genotypes were 2.36 (95% CI, 1.49-3.75), 1.20 (95% CI, 0.88-1.64) and 0.61 (95% CI, 0.34-1.12). Notably, some SNPs in VEGF-A exhibited a more pronounced effect in the triple-negative subgroup. Several SNPs in VEGF-A may be associated with improved pCR when receiving BEV in the neoadjuvant setting. Although none of the observed effects survived correction for multiple testing, our observations are consistent with previous studies on BEV efficacy in BC. Further research is warranted to clarify the predictive value of these markers. ispartof: INTERNATIONAL JOURNAL OF CANCER vol:137 issue:12 pages:2981-2988 ispartof: location:United States status: published
- Published
- 2015
43. S3-6: Neoadjuvant Chemotherapy of Paclitaxel with or without Rad001: Results of the Non-Responder Part of the GEPARQUINTO Study (GBG 44)
- Author
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C Höß, K. Schwedler, K Kittel, H. Eidtmann, Michael Untch, Hans Tesch, J Huober, Petra Krabisch, Christine Mau, Valentina Nekljudova, G. von Minckwitz, F Khandan, Peter A. Fasching, Mahdi Rezai, S. Loibl, and Claus Hanusch
- Subjects
Oncology ,Gynecology ,Cancer Research ,medicine.medical_specialty ,Everolimus ,Bevacizumab ,business.industry ,Cancer ,medicine.disease ,Interim analysis ,Lapatinib ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,skin and connective tissue diseases ,business ,medicine.drug ,Epirubicin - Abstract
Background: The oral signal transduction inhibitor everolimus (RAD001 = R), binds selectively to mTOR (mammalian target of rapamycin), an intracellular protein kinase implicated in the control of cellular proliferation of activated T-lymphocytes and neoplastic cells. Phase II data suggested that R can enhance the clinical efficacy of endocrine treatment in the metastatic and neoadjuvant setting. The GeparQuinto phase III study had 3 settings (HER2−positive: trastuzumab vs lapatinib; HER2−negative: +/− bevacizumab (Bev); HER2−negative non-responder: +/− R). Primary aim of the last setting was to improve pathological complete response (pCR) for patients with HER2−negative breast cancer not responding to 4x epirubicin/cyclophosphamide (EC) +/− Bev by adding R to weekly paclitaxel as neoadjuvant chemotherapy. Patients and Methods: Patients with untreated HER2−negative breast cancer were eligible if their tumors were stage cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1). Only patients without response ( Results: Between 11/07 and 15/06/11 402 P were randomized to Pac (N=201) and Pac+R (N=201). Median age was 51.0 and 50.0 [-R/+R] years. Median clinical tumor size was 40/40 mm; 62%/55% had cT2, 18% / 20% cT3, and 16.7% / 16.7% cT4a-d tumors; 88% / 89% had non-lobular; 35% / 33% grade 3; 55% / 57% node-positive; and 29% / 27% ER and PgR-negative (triple-negative) disease. The futility interim analysis was performed in 02/10, futility boundary was not reached and the trial was continued. After the other 2 settings completed accrual in 06/10, recruitment to the 3rd setting dropped such that it appeared not possible to recruit the full number of patients.. The trial will therefore close recruitment on June, 30th 2011 with an estimated statistical power of 65%. Results on histological response and surgical outcome will be reported. Conclusion: This will be the first report on efficacy data of neoadjuvant R + Pac for patients with early breast cancer. The results of the GeparQuinto study will have to be set into context with the results from the Bolero studies in metastatic disease. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S3-6.
- Published
- 2011
44. P1-14-05: Surgical Complications from the GeparQuinto Trial of Patients Receiving Preoperative Bevacizumab
- Author
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K. Schwedler, Hans Ulrich Ulmer, S Stirnberg, Antje Belau, K Kittel, Frank Holms, S. Loibl, Peter A. Fasching, Hans Tesch, H. Eidtmann, Christoph Salat, Iris Schrader, Valentina Nekljudova, Mahdi Rezai, Christine Mau, Minckwitz G von, Elmar Stickeler, and A Abdallah
- Subjects
Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Bevacizumab ,medicine.diagnostic_test ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,medicine.disease ,Surgery ,Hematoma ,Oncology ,Docetaxel ,Biopsy ,Medicine ,business ,Complication ,medicine.drug ,Epirubicin - Abstract
Background: Bevacizumab has been reported to increase the risk of surgical complications, especially in pts treated with neoadjuvant chemotherapy. Methods: In January 2010 it was decided to collect surgical complications prospectively on a specifically developed from. All patients received chemotherapy with epirubicin/cyclophosphamide (EC) followed by docetaxel (T) with or w/o bevacizumab. Patients not responding to the first 4 cycles of EC+/−B were enrolled in another setting. All patients receiving bevacizumab were supposed to be operated at 5 weeks after the last infusion of bevacizumab. Results: Data from 699 patients have been prospectively collected, 329 received EC-T and 370 ECB-TB. Median age was 48 years in both arms. Median tumor size was 30mm in the ET-C arm vs 35mm in the ECB-TB arm (p=0.13). Multifocal or multicentric disease was present in 21% in the EC-T arm vs 22.4% (p=0.74). 36% of the patients received a sentinel node biopsy prior to start of neoadjuvant chemotherapy in both groups. 68.7% of patients received breast conserving therapy in the EC-T arm compared to 71.1% in the ECB-TB arm (p=0.54). The rate of pathological complete response was 19.5% with EC-T compared to 23.2% with ECB-TB (p=0.26). The median time from last CHT+/− bevacizumab to surgery was 29 days in EC-T and 34 days in ECB-TB. Bleeding or hematoma were reported in 6.7% of the patients treated by EC-T and 7.1% with ECB-TB (p=0.88). Wound infections or abscess were reported in 2.5% with EC-T and 3.9% with ECB-TB (p=0.39). Delayed wound healing was reported in 3.4% with EC-T and 6.3% with ECB-TB (p=0.11). Necrosis was reported in 1.9% with EC-T and 2.5% with ECB-TB (p=0.80). Any complication was reported in 11% with EC-T compared to 15.3% with ECB-TB (p=0.12). Conclusion: In general the rate of surgical complications was low. Patients treated with bevacizumab had a numerical increase of surgical complications. However, none of the differences were statistically significant. The intervals from last infusion to surgery as defined by the study protocol appear to be safe. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-14-05.
- Published
- 2011
45. Implant-based Mesh Supported Breast Reconstruction: Patient Reported Outcome Data (PRO-BRA trial, TiLOOP® Bra) and Perspectives
- Author
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J-U Blohmer, HJ Strittmatter, Marc Thill, Marion Kiechle, A Meiré, Michael Untch, A Faridi, C Ankel, Christine Mau, E Klein, C Schumacher, R. Ohlinger, and Stefan Paepke
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Patient-reported outcome ,Radiology ,Implant ,business ,Breast reconstruction - Published
- 2018
46. TMIC-08. EXOSOMES AND ACQUIRED TREATMENT RESISTANCE IN CANCER
- Author
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Oliver D. Mrowczynski, A. B. Madhankumar, Elias Rizk, Brad E. Zacharia, Christine Mau, Becky Slagle-Webb, Russell Payne, and James D. Connor
- Subjects
Cancer Research ,business.industry ,Cell growth ,Cancer ,medicine.disease ,Microvesicles ,Abstracts ,Text mining ,Oncology ,medicine ,Cancer research ,Neurology (clinical) ,Treatment resistance ,Transfer technique ,business ,Cell survival ,Radiation resistance - Abstract
Glioblastoma Multiforme (GBM) is the most common CNS malignancy in adults, and even with multimodal therapies, carries a poor prognosis. These tumors are heterogeneous and modify their environment, promoting tumor growth, invasion, and therapeutic resistance. The intratumoral heterogeneity of GBM is accentuated during treatment. Even in the face of surgical resection and adjuvant chemoradiation, the unfortunate but inevitable recurrence and progression of GBM is nearly universal. This mechanism of acquired radiation resistance is not understood. We believe that acquired resistance of GBM is due to exosomes secreted from radiated GBM cells conferring resistance to the local cell population. Exosomes are nanometer cell-derived vesicles containing RNAs and proteins. Growing evidence demonstrates exosomes are instrumental to a cell’s interaction with its microenvironment, and have the ability to transfer information to recipient cells contributing to tumorigenicity. We utilized nanoparticle tracking analysis to analyze characteristics of exosome secretion after exposure to radiation. We used cell proliferation assays and cell survival assays to interrogate radiation derived exosome effects on the local cancer cell population. We assessed the potential of exosome blocking agents as a possible avenue for therapeutic manipulation to abrogate this oncogenic effect. We demonstrate that resistance and proliferative factors in GBM derived exosomes change after radiation exposure. Moreover, radiation derived exosomes have functional impact on tumor cell proliferation and radiation resistance. We also demonstrate the therapeutic potential of exosome blocking agents to inhibit acquired resistance, which develops in nearly all GBM patients. Radiation-derived exosomes cause increases in cellular proliferation and survival in the local cancer cell population and may be the hidden mediators of an ultimately radiation resistant tumor recurrence and the dire prognosis that follows. Adjuvant therapy with exosome blocking agents may be used to inhibit these oncogenic effects, leading to optimal patient outcomes.
- Published
- 2017
47. Famous head injuries of the first aerial war: deaths of the 'Knights of the Air'
- Author
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Chirag D. Gandhi, Christine Mau, Prateeka Koul, Victor M. Sabourin, and Charles J. Prestigiacomo
- Subjects
Adult ,Male ,Warfare ,Head (watercraft) ,Injury control ,Aviation ,Famous Persons ,Poison control ,Ancient history ,First world war ,Battlefield ,Germany ,Traumatic head injury ,Medicine ,Craniocerebral Trauma ,Humans ,World War I ,business.industry ,General Medicine ,History, 20th Century ,Spanish Civil War ,Military Personnel ,Italy ,Aerospace Medicine ,Surgery ,Neurology (clinical) ,business ,Telecommunications - Abstract
World War I advanced the development of aviation from the concept of flight to the use of aircraft on the battlefield. Fighter planes advanced technologically as the war progressed. Fighter pilot aces Francesco Baracca and Manfred von Richthofen (the Red Baron) were two of the most famous pilots of this time period. These courageous fighter aces skillfully maneuvered their SPAD and Albatros planes, respectively, while battling enemies and scoring aerial victories that contributed to the course of the war. The media thrilled the public with their depictions of the heroic feats of fighter pilots such as Baracca and the Red Baron. Despite their aerial prowess, both pilots would eventually be shot down in combat. Although the accounts of their deaths are debated, it is undeniable that both were victims of traumatic head injury.
- Published
- 2015
48. Einfluss von genetischen Varianten in der VEGF-Signalkaskade auf die Rate der pathologischen Komplettremission bei Patientinnen nach neoadjuvanter Therapie mit Bevacizumab – Ergebnisse aus der randomisierten GeparQuinto-Studie
- Author
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V Müller, J-U Blohmer, Diether Lambrechts, S. Loibl, Richard M. Weinshilboum, Bernd Gerber, Matthieu Moisse, Arif B. Ekici, PA Fasching, Michael Untch, Georg Kunz, Claus Hanusch, L Wang, Mahdi Rezai, Matthias Rübner, Hans Tesch, K. Schwedler, H Eidtmann, Alexander Hein, Christian Schem, J Huober, T Van Brussel, Brigitte Rack, Christine Mau, M. W. Beckmann, Tanja Fehm, Cornelia Liedtke, S. D. Costa, G. von Minckwitz, Gilian Peuteman, Jörn Hilfrich, Valentina Nekljudova, Lothar Häberle, and K Kittel
- Published
- 2015
49. First results of a pre-planned interim analysis of a national multicentre Patient Reported Outcome Study (PRO-Bra) in breast reconstruction following mastectomy with titaniferously coated polypropylene mesh (TiloopBra)
- Author
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A Faridi, Stefan Paepke, Annette Meir, Marion Kiechle, Ralf Ohlinger, Marc Thill, Jens Uwe Blohmer, C Ankel, Anna Jäger, Christine Mau, E Klein, and Christine Gerber-Schäfer
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,General Medicine ,Interim analysis ,Surgery ,Polypropylene mesh ,Oncology ,Interim ,medicine ,Patient-reported outcome ,Breast reconstruction ,business ,Mastectomy - Published
- 2016
50. Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial
- Author
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Kristina Lübbe, Klaus Pantel, Christian Schem, Peter A. Fasching, Christine Mau, Bettina Steinbach, Michael Untch, K. Schwedler, Sibylle Loibl, Stephan Gade, Volkmar Müller, Gunter von Minckwitz, and Heidi Schwarzenbach
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Lapatinib ,Antibodies, Monoclonal, Humanized ,Real-Time Polymerase Chain Reaction ,Translational Research, Biomedical ,Breast cancer ,Trastuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,skin and connective tissue diseases ,Survival rate ,Neoadjuvant therapy ,Neoplasm Staging ,Chemotherapy ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Carcinoma, Ductal, Breast ,Case-control study ,Middle Aged ,medicine.disease ,Prognosis ,Neoadjuvant Therapy ,3. Good health ,Survival Rate ,Carcinoma, Lobular ,MicroRNAs ,Case-Control Studies ,Quinazolines ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Follow-Up Studies - Abstract
Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p
- Published
- 2014
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