Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk.

Background: The late endosomal LAMTOR complex serves as a convergence point for both the RAF/MEK/ERK and the PI3K/AKT/mTOR pathways. Interestingly, both of these signalling cascades play a significant role in the aetiology of breast cancer. Our aim was to address the possible role of genetic polymorphisms in LAMTOR2 and LAMTOR3 as genetic risk factors for breast cancer. Methodology/Results: We sequenced the exons and exon-intron boundaries of LAMTOR2 (p14) and LAMTOR3 (MP1) in 50 prospectively collected pairs of cancerous tissue and blood samples from breast cancer patients and compared their genetic variability. We found one single nucleotide polymorphism (SNP) in LAMTOR2 (rs7541) and two SNPs in LAMTOR3 (rs2298735 and rs148972953) in both tumour and blood samples, but no somatic mutations in cancerous tissues. In addition, we genotyped all three SNPs in 296 samples from the Risk Prediction of Breast Cancer Metastasis Study and found evidence of a genetic association between rs148972953 and oestrogen (ER) and progesterone receptor negative status (PR) (ER: OR = 3.60 (1.15-11.28); PR: OR = 4.27 (1.43-12.72)). However, when we additionally genotyped rs148972953 in the MARIE study including 2,715 breast cancer cases and 5,216 controls, we observed neither a difference in genotype frequencies between patients and controls nor was the SNP associated with ER or PR. Finally, all three SNPs were equally frequent in breast cancer samples and female participants (n = 640) of the population-based SAPHIR Study. Conclusions: The identified polymorphisms in LAMTOR2 and LAMTOR3 do not seem to play a relevant role in breast cancer. Our work does not exclude a role of other not yet identified SNPs or that the here annotated polymorphism may in fact play a relevant role in other diseases. Our results underscore the importance of replication in association studies

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer

European Glaucoma Society - A guide on surgical innovation for glaucoma

Prologue Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the "advent"of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us "bring benefit, not harm"and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an € add-on' to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS's Vision and Mission. Fotis Topouzis EGS President Contributors All contributors have provided the appropriate COI visible in detail at www.eugs.org/pages/guidesurgical/ This manuscript reflects the work and thoughts of the list of individuals recognized above, but importantly, it reflects EGS views on the subject matter. Its strength originates from a team effort, where a cohesive group of authors and reviewers have worked towards a common goal and now stand behind the text in its entirety. The EGS nevertheless wishes to thank the following external contributors for their additional expertise, which was particularly valuable to the development of this Surgical Guide: Amanda Bicket, Jonathan Bonnar, Catey Bunce, Kuan Hu, Sheffinea Koshy, Jimmy Le, Tianjing Li, Francisco Otarola, Riaz Qureshi, Anupa Shah, Richard Stead and Marta Toth. A particular appreciation goes to Ian Saldanha for drafting the introductory overview on Core Outcomes onchapter 8. Finally, EGS would like to acknowledge Augusto Azuara Blanco, Chair of the Scientific and Guidelines Committee, for his expertise and advisory role throughout the entire process. Luis Abegao Pinto, Centro Hospitalar Universitário Lisboa Norte Editor Gordana Sunaric Mégevand, Eye Research Centre, Adolphe de Rothschild Hospital, Geneva, Switzerland and Centre Ophtalmologique de Florissant, Geneva, Switzerland Editor Ingeborg Stalmans, Ingeborg Stalmans, University Hospitals UZ Leuven, Catholic University KU Leuven Editor Luis Abegao Pinto, Centro Hospitalar Universitário Lisboa Norte Hana Abouzeid, Clinical Eye Research Centre Adolph de Rothschild, AZ Ophthalmologie Eleftherios Anastasopoulos, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece Augusto Azuara Blanco, Centre for Public Health, Queen's University Belfast Luca Bagnasco, Clinica Oculistica, DiNOGMI University of Genoa Alessandro Bagnis, Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Joao Barbosa Breda, Faculty of Medicine of the University of Porto, Porto, Portugal. Centro Hospitalar e Universitário São João, Porto, Portugal. KULeuven, Belgium Keith Barton, University College London, Moorfields Eye Hospital Amanda Bicket, University of Michigan (Ann Arbor, MI, USA) Jonathan Bonnar, Belfast Health and Social Care Trust Chiara Bonzano, Clinica Oculistica, IRCCS Ospedale Policlinico San Martino Rupert Bourne, Cambridge University Hospital Alain Bron, University Hospital Dijon Catey Bunce, King's College London Carlo Cutolo, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Barbara Cvenkel, University Medical Centre Ljubljana Faculty of Medicine, University of Ljubljana Antonio Fea, University of Turin Theodoros Filippopoulos, Athens Vision Eye Institute Panayiota Founti, Moorfields Eye Hospital NHS Foundation Trust Stefano Gandolfi, U.O.C. Oculistica, University of Parma Julian Garcia Feijoo, Hospital Clinico San Carlos, Universidad Complutense, Madrid Gerhard Garhoefer, Medical University of Vienna, Austria David Garway Heath, Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Gus Gazzard, Moorfields Eye Hospital NHS Foundation Trust, London. Institute of Ophthalmology, University College London. Stylianos Georgoulas, Addenbrooke's, Cambridge University Hospitals Dimitrios Giannoulis, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece Franz Grehn, University Hospitals Wuerzburg Kuang Hu, NIHR Moorfields Biomedical Research Centre, London - Institute of Ophthalmology - University College London Michele Iester, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Hari Jayaram, Moorfields Eye Hospital Gauti Johannesson, Umea University Stylianos Kandarakis, National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens, Greece. Efthymios Karmiris, Hellenic Air Force General Hospital National and Kapodistrian University of Athens, G. Gennimatas Hospital, Athens Alan Kastner, Clinica Oftalmologica Pasteur, Santiago, Chile Andreas Katsanos, University of Ioannina, Greece Christina Keskini, Aristotle University of Thessaloniki, AHEPA Hospital Anthony Khawaja, Moorfields Eye Hospital and UCL Institute of Ophthalmology Anthony King, Nottingham University Hospitals NHS Trust James Kirwan, Portsmouth hospitals university NHS trust Miriam Kolko, University of Copenhagen, Copenhagen University Hospital Rigshospitalet Sheffinea Koshy, University of Galway Antoine Labbe, Quinze-Vingts ­ National Ophthalmology Hospital Jimmy Le, Johns Hopkins Bloomberg School of Public Health, Baltimore Sanna Leinonen, Tays Eye Centre, Tampere University Hospital Sophie Lemmens, University Hospitals UZ Leuven Tianjing Li, School of Medicine, University of Colorado Anschutz Medical Campus Giorgio Marchini, Clinica Oculistica, University Hospital, AOUI, Verona, Italy José Martinez De La Casa, Hospital Clinico San Carlos. Universidad Complutense Andy McNaught, Gloucestershire Eye Unit Frances Meier Gibbons, Eye Center Rapperswil, Switzerland Karl Mercieca, University Hospitals Eye Clinic, Bonn, Germany Manuele Michelessi, IRCCS - Fondazione Bietti Stefano Miglior, University of Milan Bicocca Eleni Nikita, Moorfields Eye Hospital NHS Foundation Trust Francesco Oddone, IRCCS ­ Fondazione Bietti Francisco Otarola, Universidad de La Frontera Marta Pazos, Institute of Ophthalmology. Hospital Clínic Barcelona. Researcher at Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Norbert Pfeiffer, Mainz University Medical Center Verena Prokosh, University of Cologne, Center for ophthalmology. Riaz Qureshi, Johns Hopkins Medicine, Baltimore Gokulan Ratnarajan, Queen Victoria Hospital, East Grinstead, UK Herbert Reitsamer, University Clinic Salzburg / SALK Luca Rossetti, University of Milan, ASST Santi Paolo e Carlo, Milano, Italy Ian Saldanha, Johns Hopkins Bloomberg School of Public Health, Baltimore Cedric Schweitzer, CHU Bordeaux, Univ. Bordeaux, ISPED, INSERM, U1219 - Bordeaux Population Health Research Centre, France Andrew Scott, Moorfields Eye Hospital London Riccardo Scotto, Clinica Oculistica, DiNOGMI University of Genoa Anupa Shah, Queen's University Belfast George Spaeth, Wills Eye Hospital/Sidney Kimmel Medical College/Thomas Jefferson University Richard Stead, Nottingham University Hospitals NHS Trust Francesco Stringa, University Hospital Southampton NHS FT Gordana Sunaric, Centre Ophtalmologique de Florissant, Centre de Recherche Clinique en Ophtalmologie Mémorial Adolphe de Rothschild Andrew Tatham, University of Edinburgh, Princess Alexandra Eye Pavilion Mark Toeteberg, University Hospital Zurich Fotis Topouzis, Aristotle University of Thessaloniki, AHEPA Hospital Marta Toth, Moorfields Eye Hospital NHS Foundation Trust Carlo Traverso, Clinica Oculistica, DiNOGMI University of Genoa, and IRCCS Ospedale Policlinico San Martino Anja Tuulonen, Tays Eye Centre, Tampere University Hospital Clemens Vass, Medical University of Vienna Ananth Viswanathan, Moorfields Eye Hospital NHSFT and UCL Institute of Ophthalmology Richard Wormald, UCL Institute of Ophthalmology External Reviewers American Glaucoma Society Asia-Pacific Glaucoma Society Middle East Africa Glaucoma Society World Glaucoma Society www.eugs.org/pages/externalreviewers The team of Clinica Oculistica of the University of Genoa for medical editing and illustration Luca Bagnasco Alessandro Bagnis Chiara Bonzano Carlo Cutolo Michele Iester Riccardo Scotto Carlo Travers

Obtaining Adequate Surgical Margins in Breast-Conserving Therapy for Patients with Early-Stage Breast Cancer: Current Modalities and Future Directions

Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT

Comprehensive Axillary Evaluation in Neoadjuvant Chemotherapy Patients With Ultrasonography and Sentinel Lymph Node Biopsy

There is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre–neoadjuvant CTX and post–neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN biopsy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41405/1/10434_2005_Article_6534.pd