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Fluorescence intensity was measured at 5 and 20 minutes after probe application, with ROC-derived ΔFI thresholds controlling false positive and false negative rates at ≤3%. Performance was compared with a previously developed GGT-based probe, showing improved classification stability.",{"@graph":14,"@context":76},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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probe substantially reduces the uncertain classification rate while maintaining high predictive accuracy compared with the GGT probe.",{"name":73,"@type":60,"acceptedAnswer":74},"What does the study propose for real-time margin assessment?",{"text":75,"@type":63},"A two-step ΔFI-based protocol using the α-Man probe supports accurate, real-time, and pathologist-independent assessment of resected specimens for future intraoperative margin evaluation.","https://schema.org",{"og:url":32,"og:type":78,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":80,"canonical":32},"index,follow",{"doc_id":82,"site_id":7},348999,1790151159,{"code":4,"msg":85,"data":86},"success",[87,91,95,99,104,109,114,118,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Story & 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α-mannosidase–targeted fluorescent probe for intraoperative margin assessment in breast cancer  \nHiroki Ueo1􀀍, Hiroaki Ueo1, Takako Doi2, Miki Yamaguchi3, Sadako Akashi-Tanaka4, TomokoTakamaru5, Hitoshi Tsuda6, Takuya Moriya7, Rin Yamaguchi8, Yuji Kozuka9, Takeshi Sasaki10, Ayako Gamachi11, Yuichiro Kai1, Yoko Kubota1, Shun Kunii12, Yui Nagamori12, Kyohhei Fujita13, Yasuteru Urano13,14, Yuki Ando15, Koshi Mimori15 & Takaaki Masuda16􀀍  \nDetermining an accurate intraoperative margin is essential in breast-conserving surgery (BCS) for breast cancer. This multicenter study assessed the diagnostic potential of a novel fluorescent probe targeting α-mannosidase, named the α-Man probe, in evaluating intraoperative margins. We analyzed 274 resected breast tissue samples, including malignant and benign lesions, across four institutions. Fluorescence intensity (FI) was measured 5 and 20 min following the application of the α-Man probe. Receiver operating characteristic analysis defined definitive thresholds for changes in FI (ΔFI), maintaining false positive and false negative rates at ≤ 3% . Diagnostic performance was also compared with a γ-glutamyltranspeptidase (GGT)-based fluorescent probe that we previously developed. Using 5-min ΔFI thresholds, positive, uncertain, and negative classifications were 24.1, 53.6, and 22.3%, respectively. At 20 min, these classifications improved to 28.1, 38.3, and 33.6%, respectively. At 5 and 20 min, positive predictive values were 93.9% and 94.8%, whereas negative predictive values were 95.1% and 96.7%, respectively. Compared with theGGT probe, α-Man substantially reduced the uncertain classification rate while maintaining high predictive accuracy. This study demonstrated that a two-step ΔFI-based protocol using the α-Man probe enables the accurate, real-time, and pathologistindependent assessment of resected specimens, supporting its future application to intraoperative margin evaluation during BCS.  \nKeywords Breast cancer, Breast-conserving surgery, Surgical margin assessment, Intraoperative fluorescence diagnosis, α-mannosidase  \nBreast cancer (BC) is the most common malignancy among women, with incidence increasing annually1. Standard treatment for BC involves breast-conserving surgery (BCS) followed by radiation therapy2. An accurate intraoperative assessment of surgical margins during BCS is crucial to minimize reoperation and local recurrence rates3–7, and intraoperative frozen section analysis (IFSA) is currently widely employed owing to its  \n1Ueo Breast Cancer Hospital, 1-3-5 Futamatamachi, Oita 870-0887, Japan. 2Breast Cancer Center, Shonan Memorial Hospital, Kamakura 248-0027, Japan. 3Department of Breast Surgery, JCHO Kurume General Hospital, Kurume 830- 0013, Japan. 4Department of Breast Surgery, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, Japan.  \n5Department of Breast Surgery, SHOWA University Koto Toyosu Hospital, Tokyo 135-8577, Japan. 6Department of Basic Pathology, National Defense Medical College, Tokorozawa 359-8513, Japan. 7Department of Pathology, Kawasaki Medical School, Kurashiki 701-0192, Japan. 8Department of Diagnostic Pathology, Nagasaki University Hospital, Nagasaki 852-8501, Japan. 9Department of Pathology, Mie University Hospital, Tsu 514-8507, Japan.  \n10Department of Next-Generation Pathology Information and Networking, Faculty of. Medicine, The University of Tokyo, Tokyo 113-0033, Japan. 11Department of Pathology, Oita Oka Hospital, Oita 870-0192, Japan. 12Goryo Chemical Inc, Kita 8 Nishi 18-35-100, Chuo-ku, Sapporo 060-0008, Japan. 13Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. 14Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. 15Department of Surgery, Kyushu University Beppu Hospital, Beppu 874- 0838, Japan. 16Department of Breas","cbCaieoZ3oglVnCs","https://ap.wps.com/l/cbCaieoZ3oglVnCs","pdf",1924987,11,"English","# Background\n## Clinical need for intraoperative margin assessment in BCS\n## Limitations of frozen section analysis\n# Fluorescence-guided detection approach\n## Advantages over IFSA\n## Prior GGT-based fluorescent probe and its limitations\n# Rationale for α-mannosidase targeting\n## Glycosidase-based probe development\n## Selection of the α-Man probe\n# Study design and evaluation\n## Multicenter sample analysis and institutions\n## Fluorescence intensity measurement and ROC thresholding\n## Diagnostic performance at 5 and 20 minutes\n## Comparison with the GGT probe","[{\"question\":\"What surgical problem does this study target?\",\"answer\":\"It targets accurate intraoperative margin assessment during breast-conserving surgery to reduce reoperation and local recurrence risks.\"},{\"question\":\"How is the α-Man probe evaluated in this multicenter work?\",\"answer\":\"Fluorescence intensity is measured 5 and 20 minutes after applying the α-Man probe, and ROC analysis defines ΔFI thresholds for margin classification.\"},{\"question\":\"How does the α-Man probe compare with the previously developed GGT-based probe?\",\"answer\":\"The α-Man probe substantially reduces the uncertain classification rate while maintaining high predictive accuracy compared with the GGT probe.\"},{\"question\":\"What does the study propose for real-time margin assessment?\",\"answer\":\"A two-step ΔFI-based protocol using the α-Man probe supports accurate, real-time, and pathologist-independent assessment of resected specimens for future intraoperative margin evaluation.\"}]","Multicenter ex vivo evaluation of an α-mannosidase–targeted fluorescent probe for intraoperative margin assessment in breast cancer | PDF",1790081105,28]