Publications
272 results found
O'Keefe SJ, Li JV, Lahti L, et al., 2015, Fat, fibre and cancer risk in African Americans and rural Africans, Nature Communications, Vol: 6, Pages: 1-14, ISSN: 2041-1723
Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat, and lower fibre consumption, higher colonic secondary bile acids, lower colonic short-chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle-aged volunteers. Here we investigate further the role of fat and fibre in this association. We performed 2-week food exchanges in subjects from the same populations, where African Americans were fed a high-fibre, low-fat African-style diet and rural Africans a high-fat, low-fibre western-style diet, under close supervision. In comparison with their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis, and suppressed secondary bile acid synthesis in the African Americans.
Scott AJ, Mason SE, Arunakirinathan M, et al., 2015, Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis, British Journal of Surgery, Vol: 102, Pages: 563-572, ISSN: 0007-1323
BackgroundCurrent management of suspected appendicitis is hampered by the overadmission of patients with non-specific abdominal pain and a significant negative exploration rate. The potential benefits of risk stratification by the Appendicitis Inflammatory Response (AIR) score to guide clinical decision-making were assessed.MethodsDuring this 50-week prospective observational study at one institution, the AIR score was calculated for all patients admitted with suspected appendicitis. Appendicitis was diagnosed by histological examination, and patients were classified as having non-appendicitis pain if histological findings were negative or surgery was not performed. The diagnostic performance of the AIR score and the potential for risk stratification to reduce admissions, optimize imaging and prevent unnecessary explorations were quantified.ResultsA total of 464 patients were included, of whom 210 (63·3 per cent) with non-appendicitis pain were correctly classified as low risk. However, 13 low-risk patients had appendicitis. Low-risk patients accounted for 48·1 per cent of admissions (223 of 464), 57 per cent of negative explorations (48 of 84) and 50·7 per cent of imaging requests (149 of 294). An AIR score of 5 or more (intermediate and high risk) had high sensitivity for all severities of appendicitis (90 per cent) and also for advanced appendicitis (98 per cent). An AIR score of 9 or more (high risk) was very specific (97 per cent) for appendicitis, and the majority of patients with appendicitis in the high-risk group (21 of 30, 70 per cent) had perforation or gangrene. Ultrasound imaging could not exclude appendicitis in low-risk patients (negative likelihood ratio (LR) 1·0) but could rule-in the diagnosis in intermediate-risk patients (positive LR 10·2). CT could exclude appendicitis in low-risk patients (negative LR 0·0) and rule-in appendicitis in the intermediate group (positive LR 10·9).ConclusionRisk strati
Golf O, Strittmatter N, Karancsi T, et al., 2015, Rapid evaporative ionization mass spectrometry imaging platform for direct mapping from bulk tissue and bacterial growth media, Analytical Chemistry, Vol: 87, Pages: 2527-2534, ISSN: 0003-2700
Rapid evaporative ionization mass spectrometry (REIMS) technology allows real time intraoperative tissue classification and the characterization and identification of microorganisms. In order to create spectral libraries for training the classification models, reference data need to be acquired in large quantities as classification accuracy generally improves as a function of number of training samples. In this study, we present an automated high-throughput method for collecting REIMS data from heterogeneous organic tissue. The underlying instrumentation consists of a 2D stage with an additional high-precision z-axis actuator that is equipped with an electrosurgical diathermy-based sampling probe. The approach was validated using samples of human liver with metastases and bacterial strains, cultured on solid medium, belonging to the species P. aeruginosa, B. subtilis, and S. aureus. For both sample types, spatially resolved spectral information was obtained that resulted in clearly distinguishable multivariate clustering between the healthy/cancerous liver tissues and between the bacterial species.
Kontovounisios C, Kinross J, Tan E, et al., 2015, Complete mesocolic excision in colorectal cancer: a systematic review, COLORECTAL DISEASE, Vol: 17, Pages: 7-16, ISSN: 1462-8910
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- Citations: 74
Currie A, Varsani N, Swift P, et al., 2015, The Impact of Chronic Kidney Disease on Postoperative Outcome Following Colorectal Cancer Surgery, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 180-180, ISSN: 0007-1323
Kontovounisios C, Baloyiannis Y, Kinross J, et al., 2014, Modified right colon inversion technique as a salvage procedure for colorectal or coloanal anastomosis, COLORECTAL DISEASE, Vol: 16, Pages: 971-975, ISSN: 1462-8910
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- Citations: 11
Villasenor A, Kinross JM, Li JV, et al., 2014, <SUP>1</SUP>H NMR Global Metabolic Phenotyping of Acute Pancreatitis in the Emergency Unit, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 5362-5375, ISSN: 1535-3893
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- Citations: 19
Purkayasthas S, Penney NC, Kinross JM, et al., 2014, THE ROLE OF BILE ACIDS FOLLOWING METABOLIC SURGERY, 19th World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disorders (IFSO), Publisher: SPRINGER, Pages: 1293-1294, ISSN: 0960-8923
Mirnezami R, Jimenez B, Li JV, et al., 2014, Rapid Diagnosis and Staging of Colorectal Cancer via High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy of Intact Tissue Biopsies, Annals of Surgery, Vol: 259, Pages: 1138-1149, ISSN: 0003-4932
Objective: To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Background: Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy.Methods: Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis.Results: A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage.Conclusions: HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeu
Kinross J, Li J, Lahti L, et al., 2014, A High Fat Lower Fiber Dietary Intervention Perturbs the Urinary Metabonome and Gut Microbial Co-Metabolic Processes in a Population of African and African Americans, 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S543-S544, ISSN: 0016-5085
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- Citations: 1
Kinross J, Li J, Lahti L, et al., 2014, Su2092 A High Fat Lower Fiber Dietary Intervention Perturbs the Urinary Metabonome and Gut Microbial Co-Metabolic Processes in a Population of African and African Americans, Gastroenterology, Vol: 146, ISSN: 0016-5085
Kinross J, Muirhead LJ, Mirnezami R, et al., 2014, Microbiome-Metabonome Linked Analysis of Ascending Colon Cancer by 1HNMR MAS Spectrometry and 16S rRNA Gene Analysis (Metataxonomics), 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S688-S688, ISSN: 0016-5085
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- Citations: 1
Kinross J, Li JV, Muirhead LJ, et al., 2014, Nutritional modulation of the metabonome: applications of metabolic phenotyping in translational nutritional research, CURRENT OPINION IN GASTROENTEROLOGY, Vol: 30, Pages: 196-207, ISSN: 0267-1379
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- Citations: 19
Mirnezami R, Spagou K, Vorkas PA, et al., 2014, Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass spectrometry (MALDI-MSI) reveals novel cancer-associated field effects, Molecular Oncology, Vol: 8, Pages: 39-49, ISSN: 1574-7891
Matrix‐assisted laser desorption ionisation imaging mass spectrometry (MALDI‐MSI) is a rapidly advancing technique for intact tissue analysis that allows simultaneous localisation and quantification of biomolecules in different histological regions of interest. This approach can potentially offer novel insights into tumour microenvironmental (TME) biochemistry. In this study we employed MALDI‐MSI to evaluate fresh frozen sections of colorectal cancer (CRC) tissue and adjacent healthy mucosa obtained from 12 consenting patients undergoing surgery for confirmed CRC. Specifically, we sought to address three objectives: (1) To identify biochemical differences between different morphological regions within the CRC TME; (2) To characterise the biochemical differences between cancerous and healthy colorectal tissue using MALDI‐MSI; (3) To determine whether MALDI‐MSI profiling of tumour‐adjacent tissue can identify novel metabolic ‘field effects’ associated with cancer. Our results demonstrate that CRC tissue harbours characteristic phospholipid signatures compared with healthy tissue and additionally, different tissue regions within the CRC TME reveal distinct biochemical profiles. Furthermore we observed biochemical differences between tumour‐adjacent and tumour‐remote healthy mucosa. We have referred to this ‘field effect’, exhibited by the tumour locale, as cancer‐adjacent metaboplasia (CAM) and this finding builds on the established concept of field cancerisation.
Veselkov KA, Mirnezami R, Strittmatter N, et al., 2014, Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1216-1221, ISSN: 0027-8424
Mass spectrometry imaging (MSI) provides the opportunity toinvestigate tumor biology from an entirely novel biochemicalperspective and could lead to the identification of a new pool ofcancer biomarkers. Effective clinical translation of histology-drivenMSI in systems oncology requires precise colocalization of morphologicaland biochemical features as well as advanced methodsfor data treatment and interrogation. Currently proposed MSIworkflows are subject to several limitations, including nonoptimizedraw data preprocessing, imprecise image coregistration,and limited pattern recognition capabilities. Here we outline acomprehensive strategy for histology-driven MSI, using desorptionelectrospray ionization that covers (i) optimized data preprocessingfor improved information recovery; (ii) precise imagecoregistration; and (iii) efficient extraction of tissue-specific molecularion signatures for enhanced biochemical distinction of differenttissue types. The proposed workflow has been used to investigateregion-specific lipid signatures in colorectal cancer tissue. Uniquelipid patterns were observed using this approach according totissue type, and a tissue recognition system using multivariatemolecular ion patterns allowed highly accurate (>98%) identificationof pixels according to morphology (cancer, healthy mucosa,smooth muscle, and microvasculature). This strategy offers uniqueinsights into tumor microenvironmental biochemistry and shouldfacilitate compilation of a large-scale tissue morphology-specificMSI spectral database with which to pursue next-generation, fullyautomated histological approaches.
Dumas M-E, Kinross J, Nicholson JK, 2014, Metabolic Phenotyping and Systems Biology Approaches to Understanding Metabolic Syndrome and Fatty Liver Disease, GASTROENTEROLOGY, Vol: 146, Pages: 46-62, ISSN: 0016-5085
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- Citations: 122
Cesario A, Auffray C, Agusti A, et al., 2014, A systems medicine clinical platform for understanding and managing non- communicable diseases., Curr Pharm Des, Vol: 20, Pages: 5945-5956
Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.
Jimenez B, Drymousis P, Kinross J, et al., 2014, Metabonomic Profiling: A Novel Approach in Neuroendocrine Neoplasias, 11th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease, Publisher: KARGER, Pages: 227-227, ISSN: 0028-3835
Kinross JM, Drymousis P, Jimenez B, et al., 2013, Metabonomic profiling: A novel approach in neuroendocrine neoplasias, SURGERY, Vol: 154, Pages: 1185-1192, ISSN: 0039-6060
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- Citations: 24
Antcliffe DB, Veselkov K, Pearce JTM, et al., 2013, TRAJECTORY ANALYSIS OF CLINICAL VARIABLES TO IMPROVE DIAGNOSIS OF VENTILATOR ASSOCIATED PNEUMONIA IN PATIENTS Wan BRAIN INJURY, ESICM 26th Annual Congress, Publisher: SPRINGER, Pages: S312-S313, ISSN: 0342-4642
Lee H, Beales S, Kinross J, et al., 2013, The extent of rationing of surgical procedures by primary care trusts in england, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 37-37, ISSN: 0007-1323
Balog J, Sasi-Szabo L, Kinross J, et al., 2013, Intraoperative tissue identification using rapid evaporative ionization mass spectrometry, Science Translational Medicine, Vol: 5, Pages: 1-11, ISSN: 1946-6234
Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near–real-time characterization of human tissue in vivo by analysis of the aerosol (“smoke”) released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.
Mirnezami R, Veselkov K, Strittmatter N, et al., 2013, Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry, 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Li J, Kinross J, Ou J, et al., 2013, A High Fat Lower Fiber Dietary Intervention Perturbs the Urinary Metabonome and Gut Microbial Co-Metabolic Processes in a Population of African and African Americans, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S348-S348, ISSN: 0016-5085
Hicks L, Walker DG, Eng D, et al., 2013, Mo1388 Urinary Metabolic Profiling of Inflammatory Bowel Disease in a South Asian Cohort, Gastroenterology, Vol: 144, Pages: S-653, ISSN: 0016-5085
Hicks L, Walker DG, Eng D, et al., 2013, Urinary Metabolic Profiling of Inflammatory Bowel Disease in a South Asian Cohort, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S653-S653, ISSN: 0016-5085
Lee H, Beales S, Kinross J, et al., 2013, The extent of rationing of surgical procedures in England, LANCET, Vol: 381, Pages: 534-535, ISSN: 0140-6736
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- Citations: 3
Jimenez B, Mirnezami R, Kinross J, et al., 2013, <SUP>1</SUP>H HR-MAS NMR Spectroscopy of Tumor-Induced Local Metabolic "Field-Effects" Enables Colorectal Cancer Staging and Prognostication, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 959-968, ISSN: 1535-3893
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- Citations: 88
Nicholson JK, Holmes E, Kinross JM, et al., 2012, Metabolic phenotyping in clinical and surgical environments, Nature, Vol: 491, Pages: 384-392, ISSN: 0028-0836
Metabolic phenotyping involves the comprehensive analysis of biological fluids or tissue samples. This analysis allows biochemical classification of a person's physiological or pathological states that relate to disease diagnosis or prognosis at the individual level and to disease risk factors at the population level. These approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide. The ultimate aim of such work is to generate information on patient biology using techniques such as patient stratification to better inform clinicians on factors that will enhance diagnosis or the choice of therapy. There have been many reports of direct applications of metabolic phenotyping in a clinical setting.
Markar S, Kinross J, 2012, Authors' reply to: single-incision laparoscopic surgery (SILS) vs. conventional multiport cholecystectomy: systematic review and meta-analysis, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 26, Pages: 3000-3001, ISSN: 0930-2794
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- Citations: 1
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