114 results found
Scott AJ, Alexander JL, Merrifield CA, et al., 2019, International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis, Gut, ISSN: 0017-5749
Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.
Poynter L, Mirnezami R, Galea D, et al., 2019, Network mapping of molecular biomarkers influencing radiation response in rectal cancer, Clinical Colorectal Cancer, ISSN: 1533-0028
IntroductionPre-operative radiotherapy (RT) has an important role in the management of locally advanced rectal cancer (RC). Tumour regression following RT shows marked variability and robust molecular methods are needed with which to predict likely response. The aim of this study was to review the current published literature and employ Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC.MethodsA systematic review of electronic bibliographic databases (MEDLINE, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and non-significant results were included in the analysis. Significance was binarized based on uni- and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in rectal cancer radiation response.Results72 individual biomarkers, across 74 studies, were identified through review. On highest order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity.ConclusionsHomogenising biomarker data from original articles using controlled GO terminology demonstrates that cellular mechanisms of response to radiotherapy in RC - in particular the metabolic response to radiotherapy - may hold promise in developing radiotherapeutic biomarkers with which to predict, and in the future modulate, radiation response.
Kinross JM, 2018, Precision gaming for health: Computer games as digital medicine., Methods, Vol: 151, Pages: 28-33
Health based games have significant potential as therapeutic interventions due to the inherent mechanisms associated with social and individual game play and their capacity for sensor integration, data capture analysis and patient feedback. Moreover, they are low cost and they can be deployed at the point of care across an evolving digital ecosystem. However, a robust evidence base to support their wider adoption as a clinical intervention for chronic diseases is lacking and significant methodological barriers exist for health games developers creating efficacious 'digital medicines'. Game design is complex and it must utilise validated game mechanics balanced with a creative and engaging game design. The aim of this review is therefore to outline the fundamental steps of game development for health professionals and to critically appraise the methodology for assessing health games as medical interventions. This requires (1) The adoption of clearly defined global language for health games development based on a targeted function as therapeutic agents. (2) The development of multidisciplinary teams with a broad portfolio of development and clinical skill sets. (3) The creation of health game engines specifically built to facilitate clinical game development. (4) Robust trial design and assessment of translational impact: If games are to be prescribed, their efficacy and toxicity must be based on a rigorous assessment of their use within a real world clinical environment. Trials for precision health games have specific challenges around blinding, learning curves, bias and confounding that are particularly problematic. We propose the adoption of the IDEAL-GAMES framework for game development that systematically assess and validates games through open registries. In conclusion we propose a new framework for assessing the robustness and clinical efficacy of games for health as clinical interventions in the clinical environment.
Jitsumura M, Cunningham AL, Hitchings MD, et al., 2018, Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study, BMJ Open, Vol: 8, ISSN: 2044-6055
Background The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response.Methods and analysis This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study.Ethics and dissemination The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University’s Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared w
Pouncey AL, Scott AJ, Alexander JL, et al., 2018, Gut microbiota, chemotherapy and the host: the influence of the gut microbiota on cancer treatment, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
The gut microbiota exists in a dynamic balance between symbiosis and pathogenesis and can influence almost any aspect of host physiology. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy. The microbiota modulates the host response to chemotherapy via numerous mechanisms, including immunomodulation, xenometabolism and alteration of community structure. Furthermore, exploitation of the microbiota offers opportunities for the personalisation of chemotherapeutic regimens and the development of novel therapies. In this article, we explore the host-chemotherapeutic microbiota axis, from basic science to clinical research, and describe how it may change the face of cancer treatment.
Alexander JL, Scott AJ, Pouncey AL, et al., 2018, Colorectal carcinogenesis: an archetype of gut microbiota-host interaction, Ecancermedicalscience, Vol: 12, ISSN: 1754-6605
Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia?
Alexander JL, Scott A, Poynter LR, et al., 2018, Sa1840 - The colorectal cancer mucosal microbiome is defined by disease stage and the tumour metabonome, Digestive Disease Week 2018, Publisher: Elsevier, Pages: S415-S415, ISSN: 0016-5085
Clift AK, Kornasiewicz O, Drymousis P, et al., 2018, Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with challenging management., Endocrine Connections, Vol: 7, Pages: 268-277, ISSN: 2049-3614
Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal tumours with neuroendocrine features, and controversy exists with regards to therapeutic strategy. We undertook a retrospective review of GCC patients surgically treated at two tertiary referral centres. Clinical and histopathological data were extracted from a prospectively maintained database. Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were identified (9 females). Median age at diagnosis was 55years (range 32-77). There were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10 and 3 Tang class A, B and C tumours, respectively. Index operation was appendectomy (n=12), right hemicolectomy (n=6) or resections including appendix/right colon, omentum and the gynaecological system (n=3). Eight patients underwent completion right hemicolectomy. Surgery for recurrence included small bowel resection (n=2), debulking with peritonectomy and heated intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo-oophorectomy (all n=1). Median follow-up was 30months (range 2.5-123). One-, 3- and 5-year OS was 79.4%, 60% and 60%, respectively. Mean OS (1-, 3-, and 5-year OS) for Tang class A, B and C tumours were 73.1months (85.7%, 85.7%, 51.4%), 83.7months (all 66.7%) and 28.5months (66.7%, 66.7%, not reached), respectively. Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA, CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be clearly discriminated from relatively indolent appendiceal neuroendocrine neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA-125 are useful in detecting recurrence of GCC.
Scott AJ, Merrifield CA, Alexander JL, et al., 2017, Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK, Ecancermedicalscience, Vol: 11, ISSN: 1754-6605
The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5–6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research.Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers—such as lung and urogenital tract—was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics.On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a ‘healthy’ microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite ‘interactome’ between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may b
Galea D, Inglese P, Cammack L, et al., 2017, Translational utility of a hierarchical classification strategy in biomolecular data analytics., Scientific Reports, Vol: 7, ISSN: 2045-2322
Hierarchical classification (HC) stratifies and classifies data from broad classes into more specific classes. Unlike commonly used data classification strategies, this enables the probabilistic prediction of unknown classes at different levels, minimizing the burden of incomplete databases. Despite these advantages, its translational application in biomedical sciences has been limited. We describe and demonstrate the implementation of a HC approach for "omics-driven" classification of 15 bacterial species at various taxonomic levels achieving 90-100% accuracy, and 9 cancer types into morphological types and 35 subtypes with 99% and 76% accuracy, respectively. Unknown bacterial species were probabilistically assigned with 100% accuracy to their respective genus or family using mass spectra (n = 284). Cancer types were predicted by mRNA data (n = 1960) for most subtypes with 95-100% accuracy. This has high relevance in clinical practice where complete datasets are difficult to compile with the continuous evolution of diseases and emergence of new strains, yet prediction of unknown classes, such as bacterial species, at upper hierarchy levels may be sufficient to initiate antimicrobial therapy. The algorithms presented here can be directly translated into clinical-use with any quantitative data, and have broad application potential, from unlabeled sample identification, to hierarchical feature selection, and discovery of new taxonomic variants.
Kinross J, Mirnezami R, Alexander J, et al., 2017, A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy, Scientific Reports, Vol: 7, ISSN: 2045-2322
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis. Fusobacteria (p < 0.007) and ε- Proteobacteria (p < 0.01) were enriched on tumour when compared to adjacent normal mucosal tissue, and fusobacteria and β-Proteobacteria levels increased with advancing cancer stage (p = 0.014 and 0.002 respecitvely). Metabonomic analysis using 1H Magic Angle Spinning Nuclear Magnetic Resonsance (MAS-NMR) spectroscopy, demonstrated increased abundance of taurine, isoglutamine, choline, lactate, phenylalanine and tyrosine and decreased levels of lipids and triglycerides in tumour relative to adjacent healthy tissue. Network analysis revealed that bacteria associated with poor prognostic features were not responsible for the modification of the cancer mucosal metabonome. Thus the colon cancer mucosal microbiome evolves with cancer stage to meet the demands of cancer metabolism. Passenger microbiota may play a role in the maintenance of cancer mucosal metabolic homeostasis but these metabolic functions may not be stage specific.
Pawa N, Clift AK, Osmani H, et al., 2017, Surgical management of patients with neuroendocrine neoplasms of the appendix: appendectomy or more?, Neuroendocrinology, Vol: 106, Pages: 242-251, ISSN: 0028-3835
Background: Appendiceal neuroendocrine neoplasms (ANEN) are mostly indolent tumours treated effectively with simple appendectomy. However, controversy exists regarding the necessity of oncologic right hemicolectomy (RH) in patients with histologic features suggestive of more aggressive disease. We assess the effects of current guidelines in selecting the surgical strategy (appendectomy or RH) for the management of ANEN. Methods/Aims: This is a retrospective review of all ANEN cases treated over a 14-year period at 3 referral centres and their management according to consensus guidelines of the European and the North American Neuroendocrine Tumor Societies (ENETS and NANETS, respectively). The operation performed, the tumour stage and grade, the extent of residual disease, and the follow-up outcomes were evaluated. Results: Of 14,850 patients who had appendectomies, 215 (1.45%) had histologically confirmed ANEN. Four patients had synchronous non-ANEN malignancies. One hundred and ninety-three patients had index appendectomy. Seventeen patients (7.9%) had lymph node metastases within the mesoappendix. Forty-nine patients underwent RH after appendectomy. The percentages of 30-day morbidity and mortality after RH were 2 and 0%, respectively. Twelve patients (24.5%) receiving completion RH were found to have lymph node metastases. Two patients had liver metastases, both of them synchronous. The median follow-up was 38.5 months (range 1-143). No patient developed disease recurrence. Five- and 10-year overall survival for all patients with ANEN as the only malignancy was both 99.05%. Conclusions: The current guidelines appear effective in identifying ANEN patients at risk of harbouring nodal disease, but they question the oncological relevance of ANEN lymph node metastases. RH might present an overtreatment for a number of patients with ANEN.
Martin G, Kinross J, Hankin C, 2017, Effective cybersecurity is fundamental to patient safety, British Medical Journal, Vol: 357, ISSN: 1468-5833
Wolfer AM, Scott AJ, Rueb C, et al., 2017, Longitudinal analysis of serum oxylipin profile as a novel descriptor of the inflammatory response to surgery, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 15, ISSN: 1479-5876
Background:Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile.Methods:Adults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five).Results:Some 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HD
Kinross JM, Alexander J, Perdones-Monter A, et al., 2017, A Prospective Multi-National Study of the Colorectal Cancer Mucosal Microbiome Reveals Specific Taxonomic Changes Indicative of Disease Stage and Prognosis, DDW
Kinross J, 2017, Race-specific differences in mucosal sulfidogenic bacteria modify colon cancer risk., Gut
Alexander JL, Wilson ID, Teare J, et al., 2017, Gut microbiota modulation of chemotherapy efficacy and toxicity., Nat Rev Gastroenterol Hepatol, Vol: 14, Pages: 356-365
Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.
Inglese P, McKenzie JS, Mroz A, et al., 2017, Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of cancer, Chemical Science, Vol: 8, Pages: 3500-3511, ISSN: 2041-6539
Visual inspection of tumour tissues does not reveal the complex metabolic changes that differentiate cancer and its sub-types from healthy tissues. Mass spectrometry imaging, which quantifies the underlying chemistry, represents a powerful tool for the molecular exploration of tumour tissues. A 3-dimensional topological description of the chemical properties of the tumour permits the formulation of hypotheses about the biological composition and interactions and the possible causes of its heterogeneous structure. The large amount of information contained in such datasets requires powerful tools for its analysis, visualisation and interpretation. Linear methods for unsupervised dimensionality reduction, such as PCA, are inadequate to capture the complex non-linear relationships present in these data. For this reason, a deep unsupervised neural network based technique, parametric t-SNE, is adopted to map a 3D-DESI-MS dataset from a human colorectal adenocarcinoma biopsy onto a 2-dimensional manifold. This technique allows the identification of clusters not visible with linear methods. The unsupervised clustering of the tumour tissue results in the identification of sub-regions characterised by the abundance of identified metabolites, making possible the formulation of hypotheses to account for their significance and the underlying biological heterogeneity in the tumour.
Diederen K, Li JV, Kinross J, et al., Exclusive enteral nutrition mediates gut metabolic changes in children with Crohn’s disease, Digestive Disease Week
Alexander J, Mroz A, Perdones-Monteiro A, et al., 2016, OP165 Targeted chemical analysis of the colon cancer microbiome using desorption electrospray ionisation mass spectrometry imaging (DESI-MSI), UEGW 2016, Publisher: Sage Publications, Pages: A67-A68
Mason SE, Kinross JM, Hendricks J, et al., 2016, Postoperative hypothermia and surgical site infection following peritoneal insufflation with warm, humidified carbon dioxide during laparoscopic colorectal surgery: a cohort study with cost-effectiveness analysis., Surgical Endoscopy, Vol: 31, Pages: 1923-1929, ISSN: 0930-2794
BACKGROUND: Surgical Site Infection (SSI) occurs in 9 % of laparoscopic colorectal surgery. Warming and humidifying carbon dioxide (CO2) used for peritoneal insufflation may protect against SSI by avoiding postoperative hypothermia (itself a risk factor for SSI). This study aimed to assess the impact of CO2 conditioning on postoperative hypothermia and SSI and to perform a cost-effectiveness analysis. METHODS: A retrospective cohort study of patients undergoing elective laparoscopic colorectal resection was performed at a single UK specialist centre. The control group (n = 123) received peritoneal insufflation with room temperature, dry CO2, whereas the intervention group (n = 123) received warm, humidified CO2 (using HumiGard™, Fisher & Paykel Healthcare). The outcomes were postoperative hypothermia, SSI and costs. Multivariate analysis was performed. RESULTS: A total of 246 patients were included in the study. The mean age was 68 (20-87) and mean BMI 28 (15-51). The primary diagnosis was cancer (n = 173), and there were no baseline differences between the groups. CO2 conditioning significantly decreased the incidence of postoperative hypothermia (odds ratio 0.10, 95 % CI 0.04-0.23), with hypothermic patients found to be at increased risk of SSI (odds ratio 4.0, 95 % CI 1.25-12.9). Use of conditioned CO2 significantly decreased the incidence of SSI by 66 % (p = 0.04). The intervention group incurred costs of £155 less per patient. The incremental cost-effectiveness ratio was negative. CONCLUSION: CO2 conditioning during laparoscopic colorectal surgery is a safe, feasible and a cost-effective intervention. It improves the quality of surgical care relating to SSI and postoperative hypothermia.
Alexander J, Gildea L, Balog J, et al., 2016, A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife, Surgical Endoscopy and Other Interventional Techniques, Vol: 31, Pages: 1361-1370, ISSN: 1432-2218
Background:This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.Methods:Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy.Results:Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy.Conclusion:REIMS demonstrates high diagnostic accuracy for tumor type and for established histological featur
Kinross J, muirhead L, alexander J, et al., iKnife: Rapid evaporative ionization mass spectrometry (REIMS) enables real-time chemical analysis of the mucosal lipidome for diagnostic and prognostic use in colorectal cancer, American Association of Cancer Research, Publisher: American Association for Cancer Research, ISSN: 1538-7445
Alexander JL, Scott A, Mroz A, et al., 2016, 91 Mass Spectrometry Imaging (MSI) of Microbiome-Metabolome Interactions in Colorectal Cancer, 2016 Digestive Diseases Week, Publisher: Elsevier, Pages: S23-S23, ISSN: 0016-5085
Kinross JM, marchesi J, 2016, The Ageing Superorganism, Metabolic Phenotyping in Personalized and Public Healthcare, Editors: Nicholson, darzi, Holmes
The aging population represents one of the greatest health challenges of modern times. For the first time in history, those over the age of 60 years will outnumber children under the age of 5 years. If the quality of life and the health of this growing population are to be improved, a deeper understanding of the aging process is required. This chapter analyzes aging from a superorganism perspective; it analyzes the contribution of the vast numbers of bacteria that inhabit the gut and the impact they have on human health; it provides a systematic overview of how the “-omics” technologies are revolutionizing our understanding of the biology of aging; it assesses our current understanding of how health may be maintained in advanced aging; and it looks to the future applications of the “-omics” technologies in this area.
Kinross JM, muirhead L, takats Z, 2016, Precision surgery and surgical spectroscopy, Metabolic Phenotyping in Public and Personalised Healthcare, Editors: Nicholson, Darzi, Holmes
Surgical practice is largely based on 20th century principles, and little, if any, biological data is provided to the clinician either preoperatively or intraoperatively to assist in decision making. Therefore novel technologies are urgently required to deliver the vision of personalized health care in surgery. Metabolic phenotyping has distinct advantages over other “-omics” based technologies in surgery, as the analysis of thousands of metabolites is possible in near real time, and it is able to provide critical data on tissue phenotypes and on the functional biochemistry of surgical pathology during surgery. The inference is that surgeons, pathologists, oncologists, and physicians will be able to augment current clinical strategies with chemical analysis at the patient bedside or in the operating theater. This chapter explores emerging technologies in this field and provides practical applications of their use in several areas of surgery and perioperative care. Particular attention is paid to oncology and the application of ambient mass spectrometry technologies in this field.
Kinross J, Marchesi JR, 2016, The aging superorganism, Metabolic Phenotyping in Personalized and Public Healthcare, Pages: 265-290, ISBN: 9780128003442
© 2016 Elsevier Inc. All rights reserved. The aging population represents one of the greatest health challenges of modern times. For the first time in history, those over the age of 60 years will outnumber children under the age of 5 years. If the quality of life and the health of this growing population are to be improved, a deeper understanding of the aging process is required. This chapter analyzes aging from a superorganism perspective; it analyzes the contribution of the vast numbers of bacteria that inhabit the gut and the impact they have on human health; it provides a systematic overview of how the "-omics" technologies are revolutionizing our understanding of the biology of aging; it assesses our current understanding of how health may be maintained in advanced aging; and it looks to the future applications of the "-omics" technologies in this area.
Tekkis P, Tan E, Kontovounisios C, et al., 2015, Hand-sewn coloanal anastomosis for low rectal cancer: technique and long-term outcome, Colorectal Disease, Vol: 17, Pages: 1062-1070, ISSN: 1463-1318
AimThis study compared the operative outcome and long-term survival of three types of hand-sewn coloanal anastomosis (CAA) for low rectal cancer.MethodPatients presenting with low rectal cancer at a single centre between 2006 and 2014 were classified into three types of hand-sewn CAA: type 1 (supra-anal tumours undergoing transabdominal division of the rectum with transanal mucosectomy); type 2 (juxta-anal tumours, undergoing partial intersphincteric resection); and type 3 (intra-anal tumours, undergoing near-total intersphincteric resection with transanal mesorectal excision).ResultsSeventy-one patients with low rectal cancer underwent CAA: 17 type 1; 39 type 2; and 15 type 3. The median age of patients was 61.6 years, with a male/female ratio of 2:1. Neoadjuvant therapy was given to 56 (79%) patients. R0 resection was achieved in 69 (97.2%) patients. Adverse events occurred in 25 (35.2%) of the 71 patients with a higher complication rate in type 1 vs type 2 vs type 3 (47.1% vs 38.5% vs 13.3%, respectively; P = 0.035). Anastomotic separation was identified in six (8.5%) patients and pelvic haematoma/seroma in five (7%); two (8.3%) female patients developed a recto–vaginal fistula. Ten (14.1%) patients were indefinitely diverted, with a trend towards higher long-term anastomotic failure in type 1 vs type 2 vs type 3 (17.6% vs 15.5% vs 6.7%). The type of anastomosis did not influence the overall or disease-free survival.ConclusionCAA is a safe technique in which anorectal continuity can be preserved either as a primary restorative option in elective cases of low rectal cancer or as a salvage procedure following a failed stapled anastomosis with a less successful outcome in the latter. CAA has acceptable morbidity with good long-term survival in carefully selected patients.
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