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Yang Lv Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xu Han Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Chunyan Zhang Department of Clinical Laboratory, Zhongshan Hospital, Fudan University, Shanghai, China

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Yuan Fang Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Ning Pu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Yuan Ji Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

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Dansong Wang Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xu Xuefeng Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wenhui Lou Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Purpose

Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).

Patients and Methods

In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05.

Results

Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001).

Conclusion

CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.

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Yang Lv Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Ning Pu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wei-lin Mao Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wen-qi Chen Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Huan-yu Wang Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xu Han Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Yuan Ji Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

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Lei Zhang Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Da-yong Jin Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wen-Hui Lou Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xue-feng Xu Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Aim

We aim to investigate the clinical characteristics of the rectal NECs and the prognosis-related factors and construct a nomogram for prognosis prediction.

Methods

The data of 41 patients and 1028 patients with rectal NEC were retrieved respectively from our institution and SEER database. OS or PFS was defined as the major study outcome. Variables were compared by chi-square test and t-test when appropriate. Kaplan–Meier analysis with log-rank test was used for survival analysis and the Cox regression analysis was applied. The nomogram integrating risk factors for predicting OS was constructed by R to achieve superior discriminatory ability. Predictive utility of the nomogram was determined by concordance index (C-index) and calibration curve.

Results

In the univariate and multivariate analyses, tumor differentiation, N stage, M stage and resection of primary site were identified as independent prognostic indicators. The linear regression relationship was found between the value of Ki-67 index and the duration of OS (P < 0.05). Furthermore, the independent prognostic factors were added to formulate prognostic nomogram. The constructed nomogram showed good performance according to the C-index.

Conclusions

Contrary to WHO classification guideline, we found that the rectal NEC diseases are heterogeneous and should be divided as different categories according to the pathological differentiation. Besides, the nomogram formulated in this study showed excellent discriminative capability to predict OS for those patients. More advanced predictive model for this disease is required to assist risk stratification via the formulated nomogram.

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