Ales Ryska, Anna Sapino, Stefania Landolfi, Irene Sansano Valero, Santiago Ramon Y Cajal, Pedro Oliveira, Paolo Detillo, Luca Lianas, Francesca Frexia, Pier Andrea Nicolosi, Tommaso Monti, Benedetta Bussolati, Caterina Marchiò, Gianni Bussolati
{"title":"无乙二醛酸(GAF)组织固定剂是福尔马林的合适替代品:来自一项开放标签比较非劣效性研究的结果。","authors":"Ales Ryska, Anna Sapino, Stefania Landolfi, Irene Sansano Valero, Santiago Ramon Y Cajal, Pedro Oliveira, Paolo Detillo, Luca Lianas, Francesca Frexia, Pier Andrea Nicolosi, Tommaso Monti, Benedetta Bussolati, Caterina Marchiò, Gianni Bussolati","doi":"10.1007/s00428-023-03692-6","DOIUrl":null,"url":null,"abstract":"<p><p>Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329524/pdf/","citationCount":"0","resultStr":"{\"title\":\"Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study.\",\"authors\":\"Ales Ryska, Anna Sapino, Stefania Landolfi, Irene Sansano Valero, Santiago Ramon Y Cajal, Pedro Oliveira, Paolo Detillo, Luca Lianas, Francesca Frexia, Pier Andrea Nicolosi, Tommaso Monti, Benedetta Bussolati, Caterina Marchiò, Gianni Bussolati\",\"doi\":\"10.1007/s00428-023-03692-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.</p>\",\"PeriodicalId\":23514,\"journal\":{\"name\":\"Virchows Archiv\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329524/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Virchows Archiv\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00428-023-03692-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-023-03692-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
福尔马林是甲醛的水溶液,一个多世纪以来一直是固定组织学样品的金标准。尽管其具有相当大的优势,但越来越多的证据表明其客观毒性,特别是其致癌性和诱变作用。2016年,欧盟提出了一项禁令,但考虑到其在医疗诊断领域的重要作用,临时批准了该禁令。在本研究中,我们测试了一种创新的固定剂,无乙二醛酸(GAF)(一种不含酸的乙二醛溶液),它可以在结构和分子水平上实现最佳的组织固定,同时没有毒性和致癌活性。进行了一项开放标签、非效性、多中心的试验,比较GAF固定剂与标准磷酸盐缓冲福尔马林(PBF)固定组织学标本,通过四个由中心病理审查员和当地中心审查员回答的二元评分问题来评估形态学保存和诊断价值。GAF组和PBF固定组的平均总分分别为中心审查员3.7±0.5 vs 3.9±0.3,局部病理审查员3.8±0.5 vs 4.0±0.1。在中位数方面,两固定组的结果相似,中位数均为4.0。收集的数据表明,与PBF相比,所有器官的GAF均无劣效性。目前的临床性能研究是按照体外诊断医疗器械性能评价的国际标准进行的,突出了GAF确保制剂的结构保存和诊断价值的能力。
Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study.
Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.
期刊介绍:
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.