Clinical and Imaging Features of Neuroendocrine Tumors in Different Locations of the Gastrointestinal Tract

Background: Neuroendocrine neoplasm is a relatively common type of tumor. But the diagnosis of neuroendocrine neoplasm in gastrointestinal tract is challenging. Purpose: To investigate the clinical and imaging features of neuroendocrine tumors in different locations of the gastrointestinal tract. Material and methods: Clinical and imaging data were collected from 58 cases of gastrointestinal neuroendocrine tumors diagnosed by surgery or puncture pathology plus immunohistochemistry between January 2010 and April 2018 at the Southern Medical University Nanfang hospital. Results: In the CT plain scan, when the mass was small, it showed equal density with a clear boundary. When the mass was large, liquefaction and necrosis was apparent, and the boundary was less clear. In the contrast CT scan, the lesions continued to strengthen, showing “fast forward and slow exit”. metastasis lesions were found in lymph node (6), hepatic (9), bone (3), lung (1), adrenal (1). P values for tumors at different sites for grading, staging, Syn, CgA, and size were 0.001, 0.00, 0.006, 0.008, 0.002, and 0.000; the gender P value was 0.09. Conclusion: Differences in grading, staging, Syn and CgA expression, size, and enhancement were statistically significant (P˂ 0.05). Endocrine tumors that occur in the esophagus/stomach are more malignant than endocrine tumors of the rectum. They were significantly enhanced in duodenal lesions, but mildly enhanced in rectal lesions; With an enhancement pattern of “fast-forward and slow-out”. Imaging Features of Neuroendocrine Tumors in Different Locations of the Gastrointestinal Tract.


Introduction
Neuroendocrine neoplasms (NENs) are a group of malignant tumors that originate from neuroendocrine cells and peptidergic neurons. Gastrointestinal Neuroendocrine neoplasm is a relatively common type of neuroendocrine tumor that appears as a submucosal mass, differentiates in the direction of neuroendocrine cells of the gastrointestinal tract, and accounts for 1.2-1.5% of all of the gastrointestinal tumors [1]. The incidence of GI-NETs has recently begun to show a steady increase. Pearsow [2] reported in 1949 that a group of neuroendocrine tumors had metastasized, making people realize that neuroendocrine tumors may be malignant. Although neuroendocrine cells are located throughout the body, over 66.7% of neuroendocrine tumors appear in the gastrointestinal tract, 25% in the lungs, and the remaining 10% in other parts of the body [3]. The digestive system was the most common site of NENs, and the stomach was ranked fourth, followed by the small intestine, rectum, and pancreas [4]. As the clinical manifestation of GI-NENs is not specific, diagnosis usually occurs late in the natural course of the disease. The diagnosis of GI-NENs is quite challenging. Through the study of the clinical features and CT images of neuroendocrine tumors in different sites of the gastrointestinal tract, this paper summarizes the diagnostic features that may improve clinical diagnosis and grade of the disease.

Clinical Data
Fifty-eight cases of gastrointestinal neuroendocrine tumors diagnosed by surgery or puncture pathology and immunohistochemistry between January 2010 and April 2018, the study obtained the patients' informed consent and was approved by the clinical research ethics committee of the Southern Medical University Nanfang hospital. of which 47 cases underwent CT examination and 43 cases underwent contrast CT scan. The GE Light Speed 16 CT was utilized, and the scanning parameters were as follows: tube voltage, 120 kV; tube current 250mAs; slice thickness, 7.5 mm; slice interval, 7.5 mm; and beam pitch 1:1. The contrast-enhanced CT scan was performed using the non-ionic contrast agent Iohexol, which was injected through the elbow vein with a high-pressure syringe. The total amount was 60-100 ml, the injection flow rate was 3-5 ml/s (arterial phase, 25-30s; the portal vein, 50-60s), and the delay period was 3-5 min. After scanning, the image was transmitted to the workstation for reconstruction and analysis.
All of the images were retrospectively analyzed by two senior radiologists. The following imaging parameters were reviewed: tumor location, size, tumor margin (well-circumscribed or ill-

Pathology
Pathologic diagnosis and classification were confirmed by two physicians in the Department of Pathology of the Southern Medical University Nanfang Hospital. We performed immunohistochemical staining on the surgically resected tissues to detect the expression of Ki-67, CgA and Syn, and choose whether to determine the expression of NSE according to each individual situation. We used the Dako REALTM EnVisionTM staining system for staining. After dewaxing, hydration, and antigen retrieval of paraffin-embedded tissue, PBS was removed, and the primary antibody was added and incubated for 60 minutes at room temperature. Tissues were then rinsed with PBS 3 x for 3 min, PBS was removed, and the secondary antibody MaxVisionTM/HRP was added and incubated at room temperature for 15 min. Tissues were then rinsed 3 × for 3 min, dried, and dripped with freshly prepared DAB; tap water was used to stop color development at the appropriate time, and then the chlorophyll was re-dyed. Hydrochloric acid alcohol was used to differentiate ammonia water to blue, gradient alcohol was used for dehydration, and neutral gum was used to seal.
International standards were used to interpret the results of the immunohistochemical staining.

Statistical Analysis
Statistical analysis was performed using the SPSS 17.0 statistical software package. The mean ± standard deviation was used for counting. We compared the gender/gradation/stage/Syn/ CgA of the neuroendocrine carcinomas at different sites using the chi-square test, and then analyzed tumor size and enhancement by one-way analysis of variance; P < 0.05 was considered to be statistically significant.

Clinical Date
Fifty-eight patients were included in the study (36 males and 22 females aged 27-77 years, with an average age of 54.3 years). Of the cases, 13 occurred in the esophagus, 12 in the stomach, 14 in the small intestine, 2 in the colon, and 17 in the rectum ( Table 1)

CT Imagines
Forty-seven of the 58 patients received CT examination; 21 cases showed equal density masses and 22 showed tube wall thickening.
Lesions were less than 1 cm in 11 cases, 1-2 cm in 12 cases, and larger than 2 cm in 24 cases. In the plain scan, the smaller masses were of equal density, and the boundaries were clear. In larger masses, liquefaction necrosis occurred, and the boundary was not clear. In the enhanced scanning lesions continued to enhance, showing an enhancement pattern of "fast-forward and slowout." The venous phase showed slight enhancement in 11 cases, moderate enhancement in 19 cases, and severe enhancement in 14 cases; 6 cases had lymph node metastasis, 9 had liver metastases, 3 had bone metastases, 1 had lung metastasis, and 1 had adrenal metastasis (Figures 1-4 and Table 3).   Female, 27 years old, abdominal distension for more than 3 months, intermittent black stool for 2 days, pathological diagnosis for neuroendocrine carcinoma G2, 3A transverse CT scan + 3B transverse CT coronary artery + 3C transverse CT venous + 3D coronal CT venous phase: a swollen shadow between the pancreatic head and the duodenum, the boundary is clear, the density is uniform, the arterial phase is obviously enhanced, and the venous phase is lessened.

Statistical Results
The grading, staging, Syn, CgA, size, and enhancement P values of tumor in different sites were 0.001, 0.00, 0.006, 0.008, 0.002, and 0.000, respectively. The gender P value was 0.09 (Table 2). SEER Database analyses showed that the incidence of GEP-NENs was the highest in the small intestine, followed by the rectum, colon, stomach, and appendix. The incidence of cancer in these sites, especially in the rectum and small intestine, is

Discussion
increasing each year. a study on 25,531 patients found that the incidence of neuroendocrine tumors in males and females was close to a 1:1 ratio [5,6]. There were 58 cases in the experimental group, approximately 77.9% of which were over 40 years old, with 36 males and 22 females. The age of onset was old and men were more likely to have the disease than women, which is not consistent with other reports. The clinical symptoms and signs of these patients were not obviously specific, similar to other digestive tract tumors. Six patients exhibited no specific clinical manifestations and they were found by physical examination. Therefore, routine gastrointestinal endoscopy is helpful for the early detection of rectal neuroendocrine carcinoma. Surgery is the mainstay for the treatment of locoregional GI-NETs. Endoscopic resection is an option for well-differentiated early GI-NETs, which are thought to very rarely metastasize to lymph nodes [7].

Detection of CgA/NSE/Syn expression in tumor tissues by
immunohistochemistry is helpful for the diagnosis of NETs [8]. The most useful biomarker of neuroendocrine tumors in clinical practice has been chromogranin A, which is the product of neuroendocrine granules and can be measured in serum or plasma samples [9,10]. It has been reported that the positive expression rate of Syn is 95.62% and CgA is 77.1% in gastrointestinal endocrine tumors [11]. NET. This group did not include the pancreas, and the positive rate was lower than that reported in the literature. CgA is associated with tumor staging and metastasis and is increased in patients with metastatic disease [11,12].
Various studies have also shown that patients with larger liver metastases have higher levels of CgA. In the experimental group, the positive rate of CgA in the esophagus/stomach/small intestine was higher than that in colorectal cancers. This may be related to the larger lesions and higher grade in the esophagus/ stomach/small intestine cancers. The enzyme NSE is most useful in patients with poor NET differentiation [13]. In this group, there were 7 cases of NSE (+) and 6 cases of G3, which is consistent with Complete resection is the only treatment when the stomach is the more aggressive component [16]. of perioperative/rectal regional lymph node metastasis. The sensitivity and specificity of the standards were 66.7% and 87.5%, respectively, and the AUC was 0.844. We used lymph nodes larger than 1 cm as a predictor of lymph node metastasis, which reduced the predicted value. It is possible that some lymph nodes do not increase significantly even though metastasis has already occurred.
Therefore, the standard for metastases should be 5 mm. In NETs, the possibility of lymph node metastasis is defined by the size and depth of invasion; Lymph node dissection is useful for lesions that are at high risk for lymph node metastasis [19].
Therefore, preoperative diagnosis is essential for lymph node dissection during tumor resection. Distant metastasis of endocrine cancers of digestive tract can occur in the liver/lung/bone/adrenal gland; however, metastasis occurs most commonly in the liver.
peptide receptor radionuclide therapy (PRRT) was one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival [20].
In conclusion, CT of endocrine carcinomas of the digestive tract showed intraluminal masses or invasive wall thickening.
Esophageal/rectal lesions mainly show thickening of the wall.
Duodenal/colonic lesions mainly show masses, and enhanced scanning showed duodenal lesions were obviously enhanced.
The rectal lesions were slightly enhanced and exhibited a "fastforward and slow-out" enhancement pattern, which continued to enhance. This feature can distinguish lesions from intestinal adenocarcinoma. CT examination can not only confirm the location of the tumor, but also indicate the stage and degree of the tumor.
This is a rare disease; accurate diagnosis is important to determine the treatment plan. Therefore, it is necessary to perform CT examination on patients before surgery.

Authors 'Contributions
Xiaofeng He conceived and designed the study. Jincheng Li collected datas, Bihong Xu provided administrative support.
Shuiying Tang wrote the manuscript. All authors read and approved the manuscript.