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Cardiovascular assessment of oncological patients suggests that cancer can lead to subclinical damage of the heart. The aim of the present study was to analyze the value of baseline cardiovascular biomarkers in patients with newly diagnosed colon cancer prior to treatment. Additionally, another aim was to establish baseline cut-off alert values for this low-intensity neoplastic damage. A total of 51 patients with newly diagnosed colon cancer, without history of cardiac disease, were enrolled in a prospective, cross-sectional study. All patients underwent clinical, biochemical and basic echocardiographic evaluation before starting treatment. Patients were assessed for myocardial damage using high-sensitivity troponin T (hs-TnT), creatine kinase-MB (CK-MB) and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A group of 28 healthy controls was included for comparison. Cardiac ultrasound revealed similar left ventricular (LV) ejection fraction but enlarged LV chambers compared with the control group (LV at end systole, 29.50 vs. 26.00 mm; LV at end diastole, 44.50 vs. 38.00 mm; P<0.001 in both cases). The levels of cardiovascular biomarkers of myocardial damage were higher in the patients than in the control group (CK-MB, 17.00 vs. 11.00 IU/l, P<0.001; hs-TnT, 8.20 vs. 3.00 ng/l, P<0.001; NT-proBNP, 155.40 vs. 48.50 pg/ml, P=0.001). In multivariate analysis, CK-MB and hs-TnT retained statistical significance (P=0.004 and P=0.045, respectively). Moreover, it was demonstrated that new cut-offs for hs-TnT (8.00 ng/l) and NT-proBNP (220.00 pg/ml) can identify cardiac damage in patients ≥65 years old. Thus, the present study confirmed the hypothesis that a basic cardiovascular assessment of treatment-naïve patients with colon cancer can identify important pre-treatment myocardial impact. Adapted cut-off values should be set for cardiovascular biomarkers in the cancer population, different from those currently accepted for acute coronary syndromes or heart failure.
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Surface-enhanced Raman scattering (SERS) is emerging as a novel strategy for biofluid analysis. In this review, we delineate four experimental SERS protocols that are frequently used for the profiling of biofluids: 1) liquid SERS for the detection of purine metabolites; 2) iodide-modified liquid SERS for the detection of proteins; 3) dried SERS for the detection of both purine metabolites and proteins; 4) resonant Raman for the detection of carotenoids. To explain the selectivity of each experimental SERS protocol, we introduce a heuristic model for the chemisorption of analytes mediated by adsorbed ions (adions) onto the SERS substrate. Next, we show that the promising results of SERS liquid biopsy stem from the fact that the concentration levels of purine metabolites, proteins and carotenoids are informative of the cellular turnover rate, inflammation, and oxidative stress, respectively. These processes are perturbed in virtually every disease, from cancer to autoimmune maladies. Finally, we review recent SERS liquid biopsy studies and discuss future steps that are required for translating SERS in the clinical setting.
Assuntos
Neoplasias , Análise Espectral Raman , Humanos , Biópsia Líquida , ProteínasRESUMO
As colorectal cancer (CRC) is one of the forms of cancer with the highest prevalence globally and with a high mortality, screening and early detection remains a major issue. Colonoscopy is still the gold standard for detecting premalignant lesions, but it is burdened by some complications. For instance, it is laborious, with some difficulties of acceptance for some patients, and is ultimately an imperfect standard, given that some premalignant lesions or incipient malignancies can be missed by colonoscopic evaluation. In this context, new non-invasive approaches such as surface-enhanced Raman spectroscopy (SERS) based liquid biopsy have gained ground in recent years, showing promising results in oncological pathology diagnosis. These new methods have enabled the detection of subtle molecular profile alterations prior to any macroscopic morphological changes, thus providing a useful tool for early CRC detection. In the present review, we provide a summary of published studies applying SERS in CRC detection, along with our personal experience in using SERS in the diagnosis of different oncological pathologies, including CRC.
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Early diagnosis based on screening is recognized as one of the most efficient ways of mitigating cancer-associated morbidity and mortality. Therefore, reliable but cost-effective methodologies are needed. By using a portable Raman spectrometer, a small and easily transportable instrument, the needs of modern diagnosis in terms of rapidity, ease of use and flexibility are met. In this study, we analyzed the diagnostic accuracy yielded by the surface-enhanced Raman scattering (SERS)-based profiling of serum, performed with a portable Raman device operating in a real-life hospital environment, in the case of 53 patients with gastrointestinal tumors and 25 control subjects. The SERS spectra of serum displayed intense bands attributed to carotenoids and purine metabolites such as uric acid, xanthine and hypoxanthine, with different intensities between the cancer and control groups. Based on principal component analysis-quadratic discriminant analysis (PCA-QDA), the cancer and control groups were classified with an accuracy of 76.92%. By combining SERS spectra with general inflammatory markers such as C-reactive protein levels, neutrophil counts, platelet counts and hemoglobin levels, the discrimination accuracy was increased to 83.33%. This study highlights the potential of SERS-based liquid biopsy for the point-of-care diagnosis of gastrointestinal tumors using a portable Raman device operating in a clinical setting.
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BACKGROUND: The "watch and wait" approach has recently been proposed as an alternative to surgery in locally-advanced rectal cancer patients that respond to neo-adjuvant chemoradiotherapy, in order to decrease its negative functional consequences upon the quality of life of these patients. Current methods show low accuracy for the identification of complete responders. MATERIALS AND METHODS: A review of the literature was conducted for articles published up to March 31th, 2019. Relevant studies were identified using bibliographic searches of Pubmed database. The keywords that were used in various combinations were: "neoadjuvant chemoradiotherapy", "non-operative management", "complete pathological response", "rectal cancer", "biomarkers", "staging". RESULTS: Magnetic resonance imaging can identify complete responders with a high accuracy using new protocols like diffusion weighted imaging. Positron emission tomography with 18-fluoro-deoxy-glucose shows a sensitivity of 90.9% and specificity of 80.3% for the prediction of complete pathologic response using the change in standardized uptake value. A panel of 15 metabolites was identified and shows potential to discriminate patient resistance and sensitivity to neo-adjuvant therapy (Area Under the Curve 0.80). Furthermore, pre-treatment peripheral blood neutrophil to lymphocyte ratio below 2 and platelet to lymphocyte ratio below 133.4 are significantly correlated with good tumor response (OR 2.49). Analysis of the pattern of carcinoembryonic antigen (CEA) clearance after neoadjuvant treatment conclude that an exponential decrease of the CEA levels is associated with significant tumor down staging and complete pathologic response. CONCLUSION: New methods of assessing the response to neo-adjuvant therapy in locally-advanced rectal cancer have emerged, showing promising results. Further studies need to assess the best combination between imaging and these biomarkers in order to increase the accuracy and standardize the criteria for non-operative management. KEY WORDS: Biomarkers, Complete pathologic response, Non-Operative management, Rectal cancer, Staging.