Abdominal Imaging

ª Springer Science+Business Media, LLC 2012 Published online: 5 February 2012

Abdom Imaging (2012) 37:738–745 DOI: 10.1007/s00261-011-9836-4

CT and enhanced CT in diagnosis of gastrointestinal neuroendocrine carcinomas Dan Wang, Guo-Bin Zhang, Lei Yan, Xiao-Er Wei, Yu-Zhen Zhang, Wen-Bin Li Shanghai Jiao Tong University Medical Imaging Institute, Institute of Diagnostic and Interventional Radiology, The Sixth Affiliated People’s Hospital, Shanghai Jiao Tong University, No. 600, Yi Shan Road, Shanghai 200233, China

Abstract Objectives: To enhance diagnosis of gastrointestinal neuroendocrine carcinomas using CT and contrastenhanced CT images. Methods: A total of 44 patients with gastrointestinal neuroendocrine carcinomas, as confirmed by clinical pathology and immunohistochemistry in the Sixth Affiliated People’s Hospital of Shanghai Jiao Tong University Shanghai China, were included in the study. CT and enhanced CT scanning were performed, and the resulting images were reviewed and analyzed. Results: Twenty-seven males and 17 females were enrolled. Gastrointestinal involvement included the following: 5 cases located in the middle or inferior segment of the esophagus; 5 in the gastric cardia, 15 in the body of stomach, 6 located in the gastric antrum; 5 located in the Vater papilla of the duodenum; and 8 located in the colon. Among the 44 cases 80%–90% of the lesions had homogeneous density. Totally 81.8% (36/44) cases demonstrated homogeneous enhancement in arterial phases, most of the cases (n = 33) moderately or obviously enhanced. Only 17.2% (8/44) cases appeared as heterogeneous enhancement. And 86.4% cases (n = 38) were further enhanced in the venous phase. The CT images also revealed some of the metastases. Some liver metastasis cases have obvious homogeneous enhancement. Conclusions: CT and enhanced CT provide useful information regarding gastrointestinal neuroendocrine carcinomas’ location, density, enhancement pattern, and some metastasis. These features are helpful to increase the diagnostic accuracy. Key words: Gastrointestinal neuroendocrine carcinomas—Computed tomography—Contrast enhancement

Correspondence to: Wen-Bin Li; email: liwenbin.stju.edu.cn@hotmail. com

Gastrointestinal neuroendocrine tumors (NETs) are rare neoplasms originating from the diffuse neuroendocrine system. They are believed to be derived from endocrinecommitted immature stem cells, involving 15 types of highly differentiated ectodermal cells [1, 2]. Neuroendocrine carcinoma was a sub-class of the NETs. According to the World Health Organization classification of the NETs in 2000 and in 2010, neuroendocrine carcinomas include two kinds of the NETs. One is well-differentiated endocrine carcinoma (malignant carcinoma) with lowgrade malignant behavior, deeply invasive or with metastases. Another kind is poorly differentiated endocrine carcinoma (small-cell carcinoma), high-grade malignant. Thus, those previously called gastrointestinal malignant carcinoids, which had malignant features, are now called poorly differentiated gastrointestinal neuroendocrine carcinomas [3–8].The symptoms of the gastrointestinal endocrine carcinomas are non-specific. These may be obstruction or abdominal pain, hematemesis or hematochezia, or some neuroendocrine symptoms. Most of the gastrointestinal endocrine carcinomas lack secretion of identified peptide hormones. Only very few cases have the neuroendocrine related symptoms [9–12]. The incidence of these gastrointestinal neuroendocrine carcinomas was low. Recent reports indicate a rise, which is probably due to improvements of diagnostic method. Multi-slice CT technology and the wide use of enhanced CT scanning have provided a new approach for identifying gastrointestinal neuroendocrine carcinomas. In this study, we present 44 cases of gastrointestinal neuroendocrine carcinomas and highlight the associated CT features [13].

Methods Patients We retrospectively analyzed our database of all patients who underwent CT scanning at the Shanghai Sixth People’s Hospital Affiliated with Shanghai Jiao Tong

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University from January 2000 to June 2011. 44 (27 males, 17 females) cases out of over 200,000 surgically resected gastrointestinal patients were definitively diagnosed with as postoperatively by pathological examination and immunohistochemistry. The patients ranged in age between 51 and 89 years, with the exception of a few patients aged 27, 30, 35 years, and another aged 41 years. Nineteen patients complained of abdominal pain or obstruction symptom as the first symptom. 22 patients complained of hematemesis or hematochezia as their first symptom. Among all the 44 patents, only 2 patients complained of neuroendocrine symptom as their first symptom, one of whom had concurrent liver tumors. Besides this patient, another patient’s first symptoms were caused by liver tumors (Table 1). Following biopsies, a metastasis from a gastrointestinal endocrine carcinoma was confirmed, with a small primary lesion. After a series of examinations, the primary gastrointestinal endocrine carcinoma tumors were discovered. The study was reviewed and approved by the Shanghai 6th People’s Hospital Affiliated with Shanghai Jiao Tong University.

slices was either 5 or 7 mm. Each patient had received the contrast agent iopromide (dose, 50–70 mL) through the median cubital vein. Both the arterial phase and venous phase scanning were processed. The arterial phase scan was produced approximately 30 s after the start of the injection. The venous phase scan was produced approximately 60 s after the start of the injection.

Results Clinical findings The 44 cases comprised 27 men and 17 women. All 44 patients had experienced symptoms ranging from days to months. All the cases located in the esophagus and duodenum tended to have the obstruction and abdominal pain symptoms. Besides that, 7 cases in the stomach and 2 in the colon also had the obstruction and abdominal pain symptoms too. Totally, 43.2% (19/44) cases had these symptoms. 19 cases in stomach and 3 cases in colon had the hematemesis or hematochezia symptoms; these comprised 50% (22/44) of the total cases. Only 4.5% (2/44) cases had neuroendocrine symptoms and only 2.3% (1/44) appeared the metastasis symptom (Table 1).

CT scanning procedure Multi-slice CT scanning had been performed in all of the 44 cases using the LightSpeed VCT (GE) or Sensation CT (SIEMENS). All cases underwent enhanced CT scanning after standard CT scanning. The thickness of the scanning

Lesions Table 1 summarizes the location of the gastrointestinal endocrine carcinoma in the 44 patients. The distributions of the 44 patients were that: 5 located in the middle and

Table 1. Clinical data for the 44 patients with gastrointestinal neuroendocrine carcinomas Location

Number Age

Exact location

Symptom

<50 50–60 60–70 >70 Esophagus Stomach Duodenum Colon a

5

1

2

2

26

2

6

5

13

5 8

3 1

2 4

3

Obstruction and Hematemesis or Neuroendocrine Metastasis abdominal pain hematochezia symptom Middle and inferior segment Cardia, stomach body, antrum Vater papilla Appendix, ascending colon, sigmoid, rectum

5

0

0

0

7

18

1

0

5 2

0 4

0 1a

0 2a

1 patient had neuroendocrine symptoms and liver metastasis at the same time

Table 2. Detailed data from non-enhanced and enhanced CT images in the arterial phasea of 44 patients with gastrointestinal neuroendocrine carcinomas Location

Esophagus Stomach Duodenum Colon a b

Case number

5 26 5 8

Enhancement pattern Heterogeneous enhanced

Homogeneous enhancedb

Peripheral enhanced

Irregular enhanced

Slightly enhanced

Moderately enhanced

0 1 1 1

0 2 1 2

0 2 0 1

5 4 0 1

The arterial phase scan was produced approximately 30 s after the start of the injection The degree of homogeneous enhancement was obtained from the comparison of the enhanced CT and non-enhanced images

Obviously enhanced 0 17 3 3

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inferior segment of the esophagus; 5 in the gastric cardia, 15 in the body of stomach, 6 located in the gastric antrum; 5 located in the Vater papilla of duodenum; and 8 located in the colon. The detailed locations of the colon were: 1 in the appendix; 5 in the ascending colon; 1 in the sigmoid colon; and 1 in the rectum (Table 1).

CT techniques The region of interest (ROI)s’ CT value was measured. In an attempt to reduce quantum noise, measurements of large regions should be undertaken. At the same time, ROI should have a certain distance to the periphery of tissues and organs, to reduce the volume effect. The ROI should include a substantial part of as much as possible. The vague margin and central liquefaction necrosis of the tumor should not be included. Lesion sizes were measured. CT values were measured in standard CT images, arterial phase, and venous phase images (Table 2).

Discussion In previous articles, gastrointestinal neuroendocrine carcinomas were divided on an embryogenic basis into those of the foregut (esophagus, stomach, duodenum, upper jejunum), midgut (lower jejunum, ileum, appendix, cecum), and hindgut (colon and rectum) [14]. In this study, 59.1% (26/44) cases of the neuroendocrine carcinomas lesions we observed occurred in the stomach. The stomach was the most frequent gastrointestinal site of neuroendocrine carcinomas 18.2% (8/44) cases [15]. In the stomach, 19.2% of the lesions occurred in the gastric cardia; 57.7% of the lesions occurred in the body of stomach; 23.1% of the lesions occurred in the gastric antrum. More than half of the cases occurred in the body of the stomach. The colon was the second most frequent gastrointestinal site of neuroendocrine carcinomas, 18.2% (8/44) cases. Occurrence in the esophagus and duodenum was equal, with 5 cases (11.4%) each. The most common clinical signs and symptoms of gastrointestinal neuroendocrine carcinomas are intermittent intestinal obstruction, vague abdominal pain, hematemesis, or hematochezia [4, 15, 17]. In our study, only 2 cases presented with a hypersecretion syndrome, which coincides with data from other reports, where just 2 of 83 patients had hormonal syndromes. In this study, about 80%–90% of the lesions had homogeneous density. Only a few had heterogeneous density. Since these lesions typically have a rich blood supply [15, 18]; their density is generally homogeneous (Figs. 1A, 2A, 3A). Necrosis of the lesions causing uneven density was in the minority [10]. After injection of the contrast, totally 81.8% (36/44) cases demonstrated homogeneous enhancement during the arterial phase. In the esophagus, stomach, duodenum, and colon, the homogeneous enhancement ratio was 100% (5/5), 88.5%

Fig. 1. Gastrointestinal neuroendocrine carcinomas in the esophagus of a 41-year-old man. A The CT image shows the inferior segment of the esophagus wall is unevenly thickened. The density of the wall is homogeneous, and the lumen is slightly dilated. B Arterial phase image shows the thickened wall is homogeneously and obviously enhanced.

(23/26), 60% (3/5), and 62.5% (5/8), respectively. Lesions in the esophagus and stomach were more likely to appear with a homogeneous enhanced pattern [15, 19] (Figs. 1B, 2A, B, 3B). Only 17.2% (8/44) cases demonstrated heterogeneous enhancement, due to the necrotic or cystic areas in the lesions. Among these 8 cases, 3 appeared with circular enhancement, and 5 with irregular enhancement (Table 2; Figs. 4, 5B). In this study, degrees of CT value elevations between the standard CT images and the arterial phase images were calculated. As normally considered, if the CT value elevation is below 20 HU, it is considered as slightly enhanced; if it is between 20 and 40 HU, it is considered

D. Wang et al.: Diagnosis of gastrointestinal neuroendocrine carcinomas

Fig. 2. Gastrointestinal neuroendocrine carcinomas in the stomach of a 74-year-old man. Axial (A), sagittal (B), and coronal images (C) in the arterial phase demonstrate a lesion in the lesser curvature of the stomach, which is homogeneously and obviously enhanced. The lesion which has a lobulated

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surface does not cause stenosis of the stomach. It could be seen that the lesion is further enhanced in the venous phase. The CT virtual endoscopy image shows the lesion lay on one side (white arrow) (D), its surface uneven, and the other side shows the retracted gastric mucosa (black arrow) (E).

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Fig. 3. Well-differentiated endocrine carcinoma of the duodenum in an 82-year-old man. A The CT image shows enlargement of the ampulla of Vater. The density of the wall is homogeneous, and the lumen of the duodenum is dilated.

Fig. 4. Gastrointestinal neuroendocrine carcinomas’ location and their enhancement pattern.

as moderately enhanced; and if the CT value elevation is above 40 HU, it is considered as obviously enhanced [20]. Most gastrointestinal neuroendocrine carcinomas

B Arterial phase image: the thickened wall is homogeneously and moderately enhanced. C The axial and D coronal images show the lesion is further enhanced in the venous phase. Intrahepatic bile duct and the common bile duct are dilated.

are hypervascular and will be best seen in the arterial phase moderately or obviously enhanced. However, in some cases, portal venous phase imaging best demonstrates the tumors [20]. Among the 36 homogeneously enhanced cases, 3 were slightly enhanced; 10 cases were moderately enhanced; and 23 cases were obviously enhanced (Table 2). Without considering the partial volume effect in the CT value measuring, 63.9% (23/36) cases were obviously enhanced. This obviously enhanced pattern phenomenon is due to the characteristic abundant blood supply [6, 18, 21, 22]. In the arterial phase, it is characterized by a rapid and marked enhancement. These tumors’ histopathological features are similar to the neuroendocrine carcinoma in pancreas, so their enhancement pattern is similar too. These findings are in agreement with Badea et al.’s [23] finding in the pancreas. In this study, during the venous phase the contrast, about 86.4% (38 out of the 44) cases were further enhanced(Figs. 2A–D, 3B, C). In the moderately enhanced cases, this phenomenon was more obvious. The ascending

D. Wang et al.: Diagnosis of gastrointestinal neuroendocrine carcinomas

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Fig. 5. Endocrine carcinoma of the ascending colon in an 89-year-old woman. A The CT image shows uneven thickening of the wall of the ascending colon. The fat space around the lesion is blurred. There is an enlarged lymph node (white arrow). An abdominal aorta aneurysm is noted. B Arterial phase image shows the thickened wall is irregular and obviously enhanced. The enhancement pattern of the enlarged

lymph nodes is similar to the lesion of the ascending colon, so it is considered a metastatic lymph node (black arrow). C The liver metastases were observed 2 month after the operation. The lesions are obviously enhanced, partly homogeneously but obviously enhanced, and partly peripherally enhanced. Their enhancement pattern is similar to the primary colon lesion.

range of the CT value was from 3 to 40 HU. This phenomenon is in accord with Kim’s finding in the pancreas [24], but is different from Badea et al.’s [23] finding in the pancreas. He found that the contrast in the pancreas lesion was washed out compared to the surrounding parenchyma in the venous phase. This enhanced pattern difference is partly due to the different lesions and partly due to race and geography differences [4]. Multi-slice CT images have advances in detecting and diagnosing gastrointestinal neuroendocrine carcinomas.

The advent of multi-slice CT has allowed further improvements in image resolution. The advantages of the technique include: (a) the ability to perform very rapid CT, thus, reducing movement artifacts; (b) the CT reconstruction software program could be performed on the data of CT images, which enable thinner slice data to be obtained. Coronal or sagittal images can be obtained (Fig. 2B, C). The images may reveal more details of the lesions (Fig. 2E); (c) the CT images may uncover some of the metastases, such as lymph node metastasis or liver metastasis (Fig. 5A–C). Many of these features are of

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particular importance in the imaging of gastrointestinal neuroendocrine carcinomas [6, 14, 15, 19, 25]. In addition, after analyzing the CT images, we identified ways in which we could increase the sensitivity, such as changing the position of the patient. The CT scanning procedure was always performed with the patient in the supine position; consequently, the position of the gastrointestinal wall made it difficult to diagnose the presence of gastrointestinal neuroendocrine carcinoma lesions. When the patient is turned to a right or left position, the lesion may be seen clearly as a result of repositioning of the gastrointestinal tract owing to gravity. It is especially useful in depicting small enhancing neuroendocrine tumors in the stomach. Where possible, contrast-enhanced CT scanning should always be performed. Further, thin CT images can also demonstrate small gastrointestinal neuroendocrine carcinomas quite well [20, 24]. In this study, 5 cases of liver metastasis had an obvious homogeneous enhanced pattern. It was also due to its abundant blood supply feature [16, 24, 26–28]. Overall, multi-slice CT and multi-slice enhanced CT have a high detection rate in NETs. These lesions are uncommon, but when the tumors have the features of even density, moderate or obvious homogeneous enhancement in arterial phase, and further enhancement in the venous phases, gastrointestinal neuroendocrine carcinoma should be considered in developing the differential diagnosis. Especially when patients have liver metastasis of obviously homogeneous enhancement, underlying gastrointestinal neuroendocrine carcinomas should be considered [14, 21, 24]. Acknowledgment. This research was partly supported by Science and Technology Commission of Shanghai Municipality (Grant No. 08411951200).

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