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      A New Metastatic Lymph Node Classification-based Survival Predicting Model in Patients With Small Bowel Adenocarcinoma: A Derivation and Validation Study

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          Abstract

          Background

          Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis.

          Methods

          Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage.

          Results

          A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P < 0.001; external: 0.715; 95% CI, 0.674 to 0.756 vs. 0.648; 95% CI, 0.602 to 0.693, P < 0.001). Also, the nomogram showed good calibration in internal and external validation and larger net benefit than TNM staging.

          Conclusion

          We modified current N staging into a 4-level staging system based on the number of metastatic LNs: N0, no LN metastasis; N1, 1–2 metastatic LNs; N2, 3–8 metastatic LNs, and N3, >8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients.

          Highlights

          • The least examined number of lymph nodes was 16 in small bowel adenocarcinoma patients.

          • A new 4-level metastatic LNs staging was recommended: N0, no metastasis; N1, 1–2 LNs; N2, 3–8 LNs and N3, >8 LNs.

          • A nomogram with new staging showed great clinical usability than TNM staging for predicting survival of SBA patients.

          The number of examined and metastatic lymph nodes (LNs) is correlated inversely with survival of patients with small bowel adenocarcinoma (SBA). However, there was no verdict on the number of examined LNs and current staging of metastatic LNs was controversial in predicting survival of SBA. In this study, based on survival data of 6440 adults diagnosed SBA, we modified the examined LN number of 16 and introduced a new 4-level metastatic LN staging. Based on this new staging, we developed and validated a nomogram with greater clinical usability than traditional TNM staging for predicting survival of SBA patients.

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          Most cited references25

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          Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks.

          The area under the time-dependent ROC curve (AUC) may be used to quantify the ability of a marker to predict the onset of a clinical outcome in the future. For survival analysis with competing risks, two alternative definitions of the specificity may be proposed depending of the way to deal with subjects who undergo the competing events. In this work, we propose nonparametric inverse probability of censoring weighting estimators of the AUC corresponding to these two definitions, and we study their asymptotic properties. We derive confidence intervals and test statistics for the equality of the AUCs obtained with two markers measured on the same subjects. A simulation study is performed to investigate the finite sample behaviour of the test and the confidence intervals. The method is applied to the French cohort PAQUID to compare the abilities of two psychometric tests to predict dementia onset in the elderly accounting for death without dementia competing risk. The 'timeROC' R package is provided to make the methodology easily usable. Copyright © 2013 John Wiley & Sons, Ltd.
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            A method of comparing the areas under receiver operating characteristic curves derived from the same cases.

            Receiver operating characteristic (ROC) curves are used to describe and compare the performance of diagnostic technology and diagnostic algorithms. This paper refines the statistical comparison of the areas under two ROC curves derived from the same set of patients by taking into account the correlation between the areas that is induced by the paired nature of the data. The correspondence between the area under an ROC curve and the Wilcoxon statistic is used and underlying Gaussian distributions (binormal) are assumed to provide a table that converts the observed correlations in paired ratings of images into a correlation between the two ROC areas. This between-area correlation can be used to reduce the standard error (uncertainty) about the observed difference in areas. This correction for pairing, analogous to that used in the paired t-test, can produce a considerable increase in the statistical sensitivity (power) of the comparison. For studies involving multiple readers, this method provides a measure of a component of the sampling variation that is otherwise difficult to obtain.
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              ACG Clinical Guideline: Diagnosis and Management of Small Bowel Bleeding.

              Bleeding from the small intestine remains a relatively uncommon event, accounting for ~5-10% of all patients presenting with gastrointestinal (GI) bleeding. Given advances in small bowel imaging with video capsule endoscopy (VCE), deep enteroscopy, and radiographic imaging, the cause of bleeding in the small bowel can now be identified in most patients. The term small bowel bleeding is therefore proposed as a replacement for the previous classification of obscure GI bleeding (OGIB). We recommend that the term OGIB should be reserved for patients in whom a source of bleeding cannot be identified anywhere in the GI tract. A source of small bowel bleeding should be considered in patients with GI bleeding after performance of a normal upper and lower endoscopic examination. Second-look examinations using upper endoscopy, push enteroscopy, and/or colonoscopy can be performed if indicated before small bowel evaluation. VCE should be considered a first-line procedure for small bowel investigation. Any method of deep enteroscopy can be used when endoscopic evaluation and therapy are required. VCE should be performed before deep enteroscopy if there is no contraindication. Computed tomographic enterography should be performed in patients with suspected obstruction before VCE or after negative VCE examinations. When there is acute overt hemorrhage in the unstable patient, angiography should be performed emergently. In patients with occult hemorrhage or stable patients with active overt bleeding, multiphasic computed tomography should be performed after VCE or CTE to identify the source of bleeding and to guide further management. If a source of bleeding is identified in the small bowel that is associated with significant ongoing anemia and/or active bleeding, the patient should be managed with endoscopic therapy. Conservative management is recommended for patients without a source found after small bowel investigation, whereas repeat diagnostic investigations are recommended for patients with initial negative small bowel evaluations and ongoing overt or occult bleeding.
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                Author and article information

                Contributors
                Journal
                EBioMedicine
                EBioMedicine
                EBioMedicine
                Elsevier
                2352-3964
                13 June 2018
                June 2018
                13 June 2018
                : 32
                : 134-141
                Affiliations
                Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
                Author notes
                [1]

                Contributed equally to this work.

                Article
                S2352-3964(18)30186-5
                10.1016/j.ebiom.2018.05.022
                6021266
                29908920
                04787bc9-653b-43e5-a2f9-acba4377576d
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 March 2018
                : 23 April 2018
                : 17 May 2018
                Categories
                Research Paper

                small bowel carcinoma,metastatic lymph node,survival predicting model,tnm staging,sba, small bowel adenocarcinoma,ln, lymph nodes,seer, surveillance, epidemiology and end results,kaps, k-adaptive partitioning,dca, decision curve analysis,css, cause-specific survival,hr, hazard ratio,c-index, concordance index,tdroc, time-dependent receiver operating characteristic,km-weight, censoring weighting estimators,os, overall survival,auc, area under curve,ajcc, american joint committee on cancer

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