Objective: This study aimed to develop and validate a simple-to-use nomogram for early hepatocellular carcinoma (HCC) patients undergoing a preoperative consultation and doctors conducting a postoperative evaluation. Methods: A total of 2,225 HCC patients confirmed with stage I or II were selected from the Surveillance, Epidemiology, and End Results database between January 2010 and December 2015. The patients were randomly divided into two groups: a training group ( n = 1,557) and a validation group ( n = 668). Univariate and multivariate hazards regression analyses were used to identify independent prognostic factors. The Akaike information criterion (AIC) was used to select variables for the nomogram. The performance of the nomogram was validated concerning its ability of discrimination and calibration and its clinical utility. Results: Age, alpha-fetoprotein (AFP), race, the degree of differentiation, and therapy method were significantly associated with the prognosis of early HCC patients. Based on the AIC results, five variables (age, race, AFP, degree of differentiation, and therapy method) were incorporated into the nomogram. The concordance indexes of the simple nomogram in the training and validation groups were 0.707 (95% CI: 0.683–0.731) and 0.733 (95% CI: 0.699–0.767), respectively. The areas under the receiver operating characteristic (ROC) curve of the nomogram in the training and validation groups were 0.744 and 0.764, respectively, for predicting 3-year survival, and 0.786 and 0.794, respectively, for predicting 5-year survival. Calibration plots showed good consistency between the predictions of the nomogram and the actual observations in both the training and validation groups. Decision curve analysis (DCA) showed that the simple nomogram was clinically useful, and the overall survival significantly differed between low- and high-risk groups divided by the median score of the nomogram in the training group ( P < 0.001). Conclusion: A simple-to-use nomogram based on a large population-based study is developed and validated, which is a conventional tool for doctors to facilitate the individual consultation of preoperative patients and the postoperative personalized evaluation.
Gastrointestinal cancer is a leading contributor to cancer-related morbidity and mortality worldwide. Early diagnosis currently plays a key role in the prognosis of patients with gastrointestinal cancer. Despite the advances in endoscopy over the last decades, missing lesions, undersampling and incorrect sampling in biopsies, as well as invasion still result in a poor diagnostic rate of early gastrointestinal cancers. Accordingly, there is a pressing need to develop noninvasive methods for the early detection of gastrointestinal cancers. Biomedical optical spectroscopy, including infrared spectroscopy, Raman spectroscopy, diffuse scattering spectroscopy and autofluorescence, is capable of providing structural and chemical information about biological specimens with the advantages of non-destruction, non-invasion and reagent-free and waste-free analysis and has thus been widely investigated for the diagnosis of oesophageal, gastric and colorectal cancers. This review will introduce the advances of biomedical optical spectroscopy techniques, highlight their applications for the early detection of gastrointestinal cancers and discuss their limitations.
Liver cirrhosis is the terminal stage of most chronic liver conditions, with a high risk of mortality. Careful evaluation of the prognosis of cirrhotic patients and providing precise management are crucial to reduce the risk of mortality. Although the liver biopsy and hepatic venous pressure gradient (HVPG) can efficiently evaluate the prognosis of cirrhotic patients, their application is limited due to the invasion procedures. Child-Pugh score and the model for end-stage liver disease (MELD) score had been widely used in the assessment of cirrhotic prognosis, but the defects of subjective variable application in Child-Pugh score and unsuitability to all phases of liver cirrhosis in MELD score limit their prognostic values. In recent years, continuous efforts have been made to investigate the prognostic value of body fluid biomarkers for cirrhotic patients, and promising results have been reported. Since the collection of fluid specimens is easy, noninvasive, and repeatable, fluid biomarkers can be ideal indicators to predict the prognosis of cirrhosis. Here, we reviewed noninvasive fluid biomarkers in different prognostic functions, including the prediction of survival and complication development.
The diagnosis of early, small and alpha-fetoprotein (AFP)-negative primary hepatic carcinomas (PHCs) remains a significant challenge. We developed a simple and robust approach to noninvasively detect these PHCs. A rapid, high-throughput and single-tube method was firstly developed to measure serum autofluorescence and cell-free DNA (cfDNA)-related fluorescence using a real-time PCR system, and both types of serum fluorescence were measured and routine laboratory data were collected in 1229 subjects, including 353 PHC patients, 331 liver cirrhosis (LC) patients, 213 chronic hepatitis (CH) patients and 332 normal controls (NC). The results showed that fluorescence indicators of PHC differed from those of NC, CH and LC to various extents, and all of them were not associated with age, gender, or AFP level. The logistic regression models established with the fluorescence indicators alone and combined with AFP, hepatic function tests and blood cell analyses were valuable for distinguishing early, small, AFP-negative and all PHC from LC, CH, NC and all non-PHC, with areas under the receiver operating characteristic curves 0.857–0.993 and diagnostic accuracies 80.2–97.7%. Conclusively, serum autofluorescence and cfDNA-related fluorescence are able to be rapidly and simultaneously measured by our simple method and valuable for diagnosing early, small and AFP-negative PHCs, especially integrating with AFP and conventional blood tests.
Serum alpha-fetoprotein (AFP) levels elevated in benign liver diseases (BLD) represent a challenge in hepatocellular carcinoma (HCC) diagnosis. The present study aimed to develop a simple method to identify HCC in AFP-elevated liver diseases based on combining serum fluorescence and general clinical data. Serum specimens and clinical data were collected from 201 HCC and 117 BLD (41 liver cirrhosis, 76 chronic hepatitis) patients with abnormal serum AFP levels. Dual serum fluorescence (autofluorescence and cell-free DNA-related fluorescence) intensities were sequentially measured and expressed as 6 fluorescence indicators. The diagnostic value of these fluorescence and clinical data were evaluated alone and in combination by the area under receiver operating characteristic curve (AUROC). All fluorescence indicators significantly differed between HCC and BLD and some of them were more valuable for diagnosing HCC than AFP (AUROC 0.782–0.801 vs. 0.752). The diagnostic model established with fluorescence indicators, AFP, hepatic function tests and age showed that AUROC, sensitivity, specificity and accuracy were 0.958 (95% CI 0.936–0.979), 92.0%, 88.9% and 92.3%, respectively, and positive rates in AFP-negative, early and small HCCs were 73.8%, 81.6% and 74.3%, respectively. In conclusion, the combination of dual serum fluorescence, AFP, hepatic function tests and age is simple and valuable for identifying HCC in serum AFP-elevated liver diseases.
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