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      Combined Features Based on Preoperative Controlling Nutritional Status Score and Circulating Tumour Cell Status Predict Prognosis for Colorectal Cancer Patients Treated with Curative Resection

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          Abstract

          Background: The preoperative controlling nutritional status (CONUT) score and circulating tumour cell (CTC) status are associated with poor prognosis of colorectal cancer (CRC). The aim of the present study is to determine whether the combination of CONUT and CTC (CONUT-CTC) could better predict the prognosis of CRC patients treated with curative resection.

          Methods: Preoperative CONUT score was retrospectively calculated in 160 CRC patients who underwent curative resection at Zhongnan Hospital of Wuhan University from 2015 to 2017. Preoperative CTC counts were enumerated from 5 ml peripheral vein blood by a CTCBIOPSY® device. According to the preoperative CONUT and CTC status, the patients were divided into three groups: CONUT-CTC (0), CONUT-CTC (1) and CONUT-CTC (2). The relationship between CONUT score and CTC, as well as the associations of CONUT-CTC status with clinicopathological factors and survival, were evaluated.

          Results: Preoperatively, the number and positive rate of CTC were positively correlated with the preoperative CONUT score (P<0.01). An elevated CONUT-CTC score was significantly associated with deeper tumour invasion (P=0.025), lymphatic vessel invasion (P=0.002), venous invasion (P<0.001) and higher pTNM stage (P=0.033). Kaplan-Meier analysis and log-rank tests revealed significant decreases in recurrence-free survival (RFS) and cancer-specific survival (CSS) among CRC patients with CONUT-CTC score of 0, 1 and 2 (P<0.001). In pTNM stage-stratified analysis, high CONUT-CTC score was significantly associated with the poor (P<0.001) and CSS (P<0.001) of patients with stage III disease, but not correlated with the prognosis of patients with stage II disease (RFS: P=0.077; CSS: P<0.090). Further univariate and multivariate analyses showed that CONUT-CTC was an independent factor affecting patients' RFS [hazard ratio (HR)=2.66, 95% confidence interval (CI):1.79-3.96, P<0.001] and CSS (HR=3.75, 95%CI: 2.14-6.57, P<0.001). In time-dependent receiver operating characteristics (ROC) analyses, CONUT-CTC score had a higher area under the ROC curve (AUC) for the prediction of RFS and CSS than did preoperative CONUT score or CTC status.

          Conclusion: The preoperative CONUT-CTC score is associated with tumour progression and poor prognosis in patients with CRC treated with curative resection, indicating that better information on CRC prognosis could be obtained from combined preoperative host immune-nutritional status and CTC detection.

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          [Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients].

          Based on assessment of 200 malnourished cancer patients of digestive organs, a multiparameter index of nutritional status was defined to relating the risk of postoperative complications to base line nutritional status. The linear predictive model relating the risk of operative complication, mortality or both to nutritional status is given by the relation: prognostic nutritional index (PNI) = 10 Alb. + 0.005 Lymph. C., where Alb. is serum albumin level (g/100 ml) and Lymph. C. is total lymphocytes count/mm3 peripheral blood. When applied prospectively to 189 gastrointestinal surgical patients those who were malnourished and treated by TPN preoperatively, this index provided an accurate, quantitative estimate of operative risk. In general, resection and anastomosis of gastrointestinal tract can be safely practiced when the index is over 45. The same procedure may be dangerous between 45 and 40. In below 40, this kind of operation may be contraindicated. The prognostic nutritional index is useful also to know the prognosis of patients with terminal cancer. Despite practicing TPN to cancer patients with near terminal stages, if the PNI remains below 40 and total lymphocytes count remains below 1,000/mm3, the patients has high possibility to die within the next two months.
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            CONUT: A tool for Controlling Nutritional Status. First validation in a hospital population

            Background: The serious problem of hospital undernutrition is still being underestimated, despite its impact on clinical evolution and costs. The screening methods developed so far are not useful for daily clinical practice due to their low effectiveness/cost ratio. Objective:We present an screening tool for CONtrolling NUTritional status (CONUT) that allows an automatic daily assessment of nutritional status of all inpatients that undergo routine analysis. Design: The system is based on a computer application that compiles daily all useful patient information available in hospital databases, through the internal network. It automatically assesses the nutritional status taking into account laboratory information including serum albumin, total cholesterol level and total lymphocyte count. We have studied the association between the results of the Subjective Global Assessment (SGA) and Full Nutritional Assessment (FNA) with those from CONUT, in a sample of 53 individuals. Results: The agreement degree between CONUT and FNA as measured by kappa index is 0.669 (p = 0.003), and between CONUT and SGA is 0.488 (p = 0.034). Considering FNA as "gold standard" we obtain a sensitivity of 92.3 and a specificity of 85.0. Conclusions: CONUT seems to be an efficient tool for early detection and continuous control of hospital undernutrition, with the suitable characteristics for these screening functions.
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              Inflammation and cancer

              Infection and inflammation account for approximately 25% of cancer-causing factors. Inflammation-related cancers are characterized by mutagenic DNA lesions, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine. Our previous studies demonstrated the formation of 8-oxodG and 8-nitroguanine in the tissues of cancer and precancerous lesions due to infection (e.g., Opisthorchis viverrini-related cholangiocarcinoma, Schistosoma haematobium-associated bladder cancer, Helicobacter pylori-infected gastric cancer, human papillomavirus-related cervical cancer, Epstein-Barr virus-infected nasopharyngeal carcinoma) and pro-inflammatory factors (e.g., asbestos, nanomaterials, and inflammatory diseases such as Barrett’s esophagus and oral leukoplakia). Interestingly, several of our studies suggested that inflammation-associated DNA damage in cancer stem-like cells leads to cancer development with aggressive clinical features. Reactive oxygen/nitrogen species from inflammation damage not only DNA but also other biomacromolecules, such as proteins and lipids, resulting in their dysfunction. We identified oxidatively damaged proteins in cancer tissues by 2D Oxyblot followed by MALDI-TOF/TOF. As an example, oxidatively damaged transferrin released iron ion, which may mediate Fenton reactions and generate additional reactive oxygen species. Dysfunction of anti-oxidative proteins due to this damage might increase oxidative stress. Such damage in biomacromolecules may form a vicious cycle of oxidative stress, leading to cancer development. Epigenetic alterations such as DNA methylation and microRNA dysregulation play vital roles in carcinogenesis, especially in inflammation-related cancers. We examined epigenetic alterations, DNA methylation and microRNA dysregulation, in Epstein-Barr virus-related nasopharyngeal carcinoma in the endemic area of Southern China and found several differentially methylated tumor suppressor gene candidates by using a next-generation sequencer. Among these candidates, we revealed higher methylation rates of RAS-like estrogen-regulated growth inhibitor (RERG) in biopsy specimens of nasopharyngeal carcinoma more conveniently by using restriction enzyme-based real-time PCR. This result may help to improve cancer screening strategies. We profiled microRNAs of nasopharyngeal carcinoma tissues using microarrays. Quantitative RT-PCR analysis confirmed the concordant downregulation of miR-497 in cancer tissues and plasma, suggesting that plasma miR-497 could be used as a diagnostic biomarker for nasopharyngeal carcinoma. Chronic inflammation promotes genetic and epigenetic aberrations, with various pathogeneses. These changes may be useful biomarkers in liquid biopsy for early detection and prevention of cancer.
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                Author and article information

                Journal
                Int J Biol Sci
                Int. J. Biol. Sci
                ijbs
                International Journal of Biological Sciences
                Ivyspring International Publisher (Sydney )
                1449-2288
                2019
                12 May 2019
                : 15
                : 6
                : 1325-1335
                Affiliations
                [1 ]Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
                [2 ]Hubei Key Laboratory of Tumour Biological Behaviors, Wuhan 430071, China;
                [3 ]Hubei Cancer Clinical Study Center, Wuhan 430071, China;
                [4 ]Department of Equipment Research and Development, Wuhan YZY Medical Science & Technology Co., Ltd., Wuhan 430075, China.
                Author notes
                ✉ Corresponding author: Dr. Bin Xiong, MD. Email: binxiong1961@ 123456whu.edu.cn ; Tel.:+862767813152

                *These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijbsv15p1325
                10.7150/ijbs.33671
                6567813
                31223290
                a3089fde-6954-4d93-b32c-349ea2097d4e
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 30 January 2019
                : 13 March 2019
                Categories
                Research Paper

                Life sciences
                controlling nutritional status,circulating tumour cell,prognosis,colorectal cancer,curative resection

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