# Versatile Mass Spectrometry-Based Intraoperative Diagnosis of Liver Tumor in a Multiethnic Cohort  
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1 Shimadzu Italia S.r.l., [PERSON], 7, 20139 Milano, Italy; [EMAIL_ADDRESS]  
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2 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via [PERSON] 2, 2015 Milan, Italy; angela.siciliano@marionegri.it2  
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3 Department of Biomedical Science, Humanites University, Via [PERSON] 4, 20090 Piece Emanuele, Italy; [EMAIL_ADDRESS] (M.D. ); [EMAIL_ADDRESS] (A.L. ); [EMAIL_ADDRESS] (L.D.T. ); [EMAIL_ADDRESS] (G.T. ); [PERSON]  
8 Bimadzu Corporation, Kyoto 604-8511, Japan; [EMAIL_ADDRESS] (H.S. ); [EMAIL_ADDRESS] (H.N.) [PERSON]  
9 Department of Anatomy, Telkyo University School of Medicine, 2-11-1, Kaga, Iabashi, Tokyo 173-8605, Japan; [EMAIL_ADDRESS] (S.); [EMAIL_ADDRESS] (B.F.)  
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9 Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, 1110, Chuo, Yamanashi 409-3898, Japan91002221141  
survival after surgical resection ranges between 20 and 60%, depending on the liver function and histological profile [1]. The goal of surgery is to remove the whole tumors, with minimal loss of surrounding healthy tissue: this is essential to preserve the function of the target organ, without over-resecting the surrounding non-tumor tissue. Besides the higher healthcare costs, the risk of relapse would implicate physical and psychological morbidity for patients. Several approaches, such as ultrasound 3D navigation and indigo carmine staining of tissue by infusion, now permit more accurate identification of the resection border during surgery. However, because the tissue is not examined directly, the diagnosis must be considered clinical rather than definitive. On the other hand, rapid intraoperative pathology diagnosis usually fails to yield a clear and unequivocal result, leaving surgeons hesitant about a definitive decision. Furthermore, depending on the number of specimens, surgeons must hold up the surgical procedure for 15-30 min, leaving the patient under general anesthetic, which may be a problem for some patients, as well as being costly for a social medical care system. A more sensitive and quicker procedure is therefore required to improve the surgical treatment of solid tumors. The majority of current procedures, regardless of the instrumentation repertoire, are based on morphological alterations. As a result, completely alternative approaches based on the chemical fingerprinting of the tumors may interest surgeons because they provide an entirely new layer of information based on arguably more objective data. The use of mass spectrometry (MS) in clinical analysis dates back to the 1950s [2; 3], when it was first employed to identify and quantify exogenous and endogenous compounds, such as drugs, metabolites, and proteins, in tissue samples. Technological advances have led to smaller instruments capable of providing detailed molecular information from tissue samples in real-time, with minimal sample pre-treatment. The MS technology can be used for classifying tissues and provides valuable prognostic information, such as the tumor subtype and grade [4]. MS technologies for tissue analysis now give promising results in precision medicine and intraoperative evaluation of surgical margins in various cancers, such as breast, pancreas, glioma, lung, brain, and liver [5; 6; 7; 8; 9; 10; 11]. These examples mostly employ an approach based on the identification of MS signals specific to tumors, which are significantly stronger than those of non-tumor tissues. The changes usually come from alterations to the cell metabolism or tumor microenvironment. MS-based strategies have been extensively investigated as prospective clinical tools for analyzing clinical materials such as tissues and biological fluids in clinical research, as well as for preoperative and intraoperative applications.