|Year : 2016 | Volume
| Issue : 3 | Page : 119-126
The role of multislice computed tomography in the diagnosis of gastric malignant tumors
Atef H Teama1, Amr M El-Badry2, Eslam S Yousef1
1 Department of Radiodiagnosis & Medical Imaging, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Radiodiagnosis & Medical Imaging, Tanta Cancer Centre, Tanta, Egypt
|Date of Submission||11-Oct-2015|
|Date of Acceptance||20-Dec-2015|
|Date of Web Publication||19-Jan-2017|
Amr M El-Badry
Department of Radiodiagnosis & Medical Imaging, Tanta Faculty of Medicine, Tanta University, Tanta
Objective The aim of this study was to evaluate the efficacy of multislice computed tomography (MSCT) in the diagnosis and staging of gastric malignant tumors.
Patients and methods This study included 40 patients who were highly suspected clinically and/or known cases of gastric tumors referred for MSCT examination and evaluation. The MSCT data were correlated and compared with histopathological results.
Results Of those 40 patients, 39 were confirmed histopathologically to have malignant gastric tumor (39/40) (97.5%). Of those 39 patients, 36 were depicted using MSCT (36/39) with 92.3% sensitivity, and only three cases were underestimated as T0 (false negative) with MSCT. Those 39 patients were staged histopathologically as follows: T1, 10 patients; T2, nine patients; T3, six patients; and T4, 14 patients. Gastric tumor staging was also performed through MSCT, which had higher sensitivity in depiction and accurate staging of T4 (12/14) (85.7%) and T3 (5/6) (83.3%) in comparison with T2 (5/9) (55.6%) and T1 (5/10) (50%) staging. MSCT had 83.3% sensitivity in N0 staging, 60% in N1 staging, and 50% in N2 staging.
Conclusion MSCT can provide valuable additional information and improve the detection and staging of both early and advanced gastric neoplasm. MSCT offers high diagnostic accuracy in tumor detection and staging of lymph node metastasis, and high reliable information as regards secondary tumors. MSCT is a valuable tool for monitoring response to treatment and post-treatment evaluation of gastric neoplasm.
Keywords: Gastric neoplasm, malignant gastric tumors, multislice computed tomography
|How to cite this article:|
Teama AH, El-Badry AM, Yousef ES. The role of multislice computed tomography in the diagnosis of gastric malignant tumors. Tanta Med J 2016;44:119-26
|How to cite this URL:|
Teama AH, El-Badry AM, Yousef ES. The role of multislice computed tomography in the diagnosis of gastric malignant tumors. Tanta Med J [serial online] 2016 [cited 2020 Nov 29];44:119-26. Available from: http://www.tdj.eg.net/text.asp?2016/44/3/119/198480
| Introduction|| |
Gastric cancer is still the second most common cause of cancer-related death in the world. The etiology of this disease is still unknown; however, the most common predisposing factors are Helicobacter pylori infection, bad dietary habits, smoking, regular use of alcohol, and pernicious anemia .
Multislice computed tomography (MSCT) offers new opportunities in the imaging of the upper gastrointestinal tract. Its ability to cover a large volume in a very short time and in a single breath hold allows the imaging of the entire esophagus, stomach, and gastrointestinal junction with high-quality multiplanar reformation (MPR) .
Optimally timed administration of intravenous contrast material permits precise evaluation of carcinoma enhancement, and water-filling method permits negative contrast to enhance gastric walls .
Although diagnostic advancements in performing endoscopy and double-contrast barium study currently allows the detection of small lesions early in the course of the disease, the depth of tumor invasion and the presence or absence of metastases could not be determined with either modality. In a routine clinical setting, patients with esophageal and gastric carcinoma most commonly undergo diagnosis and staging with computed tomography (CT) .
MSCT scanner can be considered as a turbocharged spiral scanner. Conventional and spiral CT scanner use single-row detectors to pick up X-ray beam after it has passed through the patient. MSCT scanner has many rows of detectors and also comes with faster computer software, which offers high reconstruction and postprocessing capabilities . MSCT has allowed us to surpass most of the limitations of single-row detector spiral CT, in particular the very thin section collimation. The high speed of acquisition and the near isotropy of the voxels allow us to reformat images in any plane without substantial artifacts and with excellent anatomic details .
A key advantage of MSCT is its speed. Combining of a multirow detector array and a reduced gantry time rotation allows scanning of a very large volume very quickly and therefore opens to CT many applications that were not possible with spiral CT ,,.
The role of MSCT is to differentiate the benign and malignant gastric neoplasm, and determine the stage and gastric spread of gastric carcinoma, which is vital in choosing between palliative or radical surgical treatment. In addition, multidetector computed tomography (MDCT) is used to monitor response to treatment. Furthermore, it has been shown to be a very important prognostic factor in patients with gastric cancer by evaluation and estimation of tumor invasion depth after MPR .
MSCT is currently the staging modality of choice, because it can help identify the primary tumor, assess for focal spread and the depth of tumor invasion, and detect nodal involvement and distant metastases. Demonstration of the lesion is facilitated by negative contrast (water) .
| Patients and methods|| |
This study included 40 patients known to have gastric tumor. Nine patients were clinically suspected to have gastric tumor proved to be free from gastric lesions and were excluded from this study. The cases of gastric cancers were referred from Tanta Cancer Centre to MDCT Unit in Radiodiagnosis and Medical Imaging Department of Tanta University Hospitals for diagnosis and staging of malignant gastric tumors. This study was performed during the period from March 2010 to March 2014.
This study was approved by the local research and ethical Committee of Tanta Cancer Centre. The aim, methods, and limitation of the technique were described to every case before performing examination. The radiological procedures were performed free of cost for the patients.
Inclusion criteria: Patients who were highly suspected clinically and/or known to have gastric neoplasm were included in the study.
Exclusion criteria: Pregnant women were excluded to avoid hazards of ionizing radiation to the fetus, and those having contraindication to intravenous contrast media, such as severe allergic reaction, and terminal liver or renal failure (creatinine>2 mg/dl) were also excluded from the study.
All 40 patients of our study were subjected to the following:
- Thorough history taking, with special stress on presenting complaint such as dyspepsia, dysphagia, anemia, weight loss, hematemesis, and melena.
- Clinical examination, including general and local abdominal searching for any signs of malignancy or metastases.
- Laboratory investigations, such as complete blood count for anemia, erythrocyte sedimentation rate, bleeding parameters, renal profile, stool analysis for occult blood, serum chemistry profile to evaluate abnormal liver, and bone chemistry enzymes (e.g. ferritin, to indicate iron deficiency).
- Radiological examination: MSCT of the abdomen and pelvis was performed using 16 multirow detector scanner.
- Patient preparation: Patients were made to fast for at least 8 h before CT examination.
- Gastrografin oral contrast for 12 cases in which the gut must be evaluated for masses (6 h before CT examination).
- Intramuscular administration of anisodamine 30 min before CT to decrease peristaltic bowel movements.
- Intake of 1000–1200 ml tap water (negative contrast) for gastric filling 10–15 min before CT scan.
- Examination in supine position.
- Unenhanced CT scan of the upper abdomen, followed by intravenous nonionic contrast (150 ml of Ultravist 300 mgI/ml) by means of automatic power injector at a flow rate of 4 ml/s.
- CT acquisition in the arterial phase (start delay of 30 s), portal phase (start delay 75 s), and in equilibrium phase (start delay 180 s).
- During MDCT scanning, we restricted arterial and portal venous phase acquisition to the stomach with a section thickness of 3.75 mm. The equilibrium phase CT examination included the whole abdomen and pelvis, with a section thickness of 5 mm from dome to anal verge.
- CT scan parameters used were as follows: 120 mA; 120 kV; pitch, 3; reconstruction interval, 2.5 mm; and tube rotation time, 0.8 s. All CT data were transferred to a workstation of MPR image.
- Postprocessing technique: Images were reconstructed at 3–5 mm interval for the screening of the abdomen. Slice reconstruction was performed with a slice width of 1.25 mm and a slice interval of 1 mm as source image for MPR image and volume rendering of the stomach, which were routinely obtained in the coronal and the sagittal direction.
- Histopathological results of tru-cut (ultrasound-guided biopsy, CT-guided biopsy, or endoscopic biopsy) or postsurgical excision biopsy were considered the reference standard. Concordance between the MSCT imaging and histopathological results was documented for each lesion to minimize the chance of sampling error.
- Statistical presentation and analysis of this study was conducted using the χ2-test by SPSS, version 17 (Chicago: SPSS Inc.). The diagnostic accuracy of MSCT triphasic CT was compared with histopathological results as standard for reference through χ2-tests (P < 0.05 was considered significant).
| Results|| |
This study included 40 patients who were highly suspected clinically and/or known cases of gastric neoplasm referred for MSCT for diagnosis and evaluation. ([Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6]) represent some of those cases. The patients included 23 male and 17 female patients between 20 and 70 years of age ([Table 1]).
|Figure 1: (a–e) A male patient aged 59 Ys presented clinically with dysphagia, anemia and weight loss.(a) Barium swallow(single contrast) revealed; an irregular mural thickening of the distal segment of the esophagus and GEJ, with shouldering and regional encroaching on its lumen with 2ry proximal mild esophageal dilatation. MSCT with I.V. contrast and gastric –vecontrast(water), axial (b,c) and coronal (MPR) (d,e) revealed; diffuse irregular enhancing GIJ mural thickening involving the full thickness of the gastric wall with extramural extension, associated also with small bi-lobar hypodense hepatic deposits, also para-gastric lymph nodes are involved exhibiting CT findings of T4 stagegastro-esophageal tumor (confirmed histopathologically to be gastro-esophageal adeno-carcinoma grade II).|
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|Figure 2: (a–c) A male patient aged 54 Ys presented clinically with vomiting, pain and weigh loss. MSCT with IV contrast and water filling of stomach, axial (a,b) and coronal MPR (c) at arterial phase revealed; circumferential hetregnouslyenhanced irregular mural thickening of pyloric antrum involving gastric mucosa, sub-mucosa &musularispropria with regional an irregular encroachment on its lumen, without detectable extra- mural extension denoting T3 stage gastric tumor (confirmed histo-pathologicallyto be moderately differentiated gastric adeno-carcinoma).|
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|Figure 3: (a–d) A male patient aged 65 Ys presented clinically by dyspepsia, vomiting and weight loss. MSCT of the abdomen with IV contrast &oral gastrografine&hydro-gastric –vecontrast; axial (a,b) and coronal (MPR) (c,d) (at arterial phase) revealed; a large heterogeneously enhanced soft tissue mass involving essentially the pyloric region of the stomach with marked regional luminal encroachment, infiltrating the full thickness of gastric wall with intraluminal protrusion and extramural exophytic extension denoting T4 stage gastric tumor (confirmed histo-pathologically to be GIST).|
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|Figure 4: (a–d) A female patient aged 40 Ys presented by enlarged abdomen, abdominal pain, dyspepsia and cachexia. Abdomino-pelvic MSCT with IV &gastrografine oral contrast; axial (a,b) and coronal(MPR)(c,d) revealed; A huge complex heterogeneously enhanced right sided pelvic mass, infiltrating the Rt. ovary and uterus with displacing itcontralaterallywith visualized left adnexal cyst with mural enhancement (b), also multiple hypodensehepatic deposits (a), a large diffuse gastric mass with hetregnous density (a and d) in addition to multiple variable sized hypodense scattered peritoneal masses (c), exhibiting CT. appearance of krukenberg’s tumor (confirmed histopathologically to be metastatic ovarian carcinoma from 1ry gastricadenocarcinoma) (i.e Krukenberg’s tumor), with hepatic and peritoneal metastatic deposits.|
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|Figure 5: (a–d) A male patient aged 59 Ys presented by abdominal pain and anemia. Multi-slice CT with I.V. and oral gastrografine contrast; axial (a, b and c) and coronal (MPR) at arterial phase (D) revealed; Diffuse non enhanced gastric mural thickening, merging large non enhanced lesser sac mass with lobulated borders (a, b and d) and multiple para-aortic, coeliac and pre-caval enlarged lymph nodes (thick arrows) (c) in addition to a small hypodense non-enhancing splenic focal lesionexhibiting CT appearance of lymphoma (confirmed histopathologically to be non-Hodgkin’s lymphoma.|
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|Figure 6: (a–d) Female patient aged 63 Ys presented clinically by dyspepsia, vomiting and anemia. Abdominal MSCT with IV contrast and hydro-gastric–ve contrast; axial (a and b) and coronal (MPR) (c and d) at arterial phase revealed; circumferential gastric body irregular heterogeneously enhanced mural thickening, with encroachment on its lumen, and visualized bi-lobar hepatic hypodense non-enhancing focal lesions(arrowed), also small porta-hepatis, coeliac and para-gastric enlarged lymph nodes denoting T4 stage gastric tumor (confirmed histopathologically to be moderately differentiated gastric adeno-carcinoma grade II), with hepatic and nodal metastatic deposits.|
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We found that male patients were more affected [23/40] [57.5%] compared with female patients [17/40] [42.5%], and the sixth decade group was the most affected one [17/40] [42.5%], followed by the fifth [11/40] [27.5%] and seventh [10/40] [25%] decade groups.
All 40 patients underwent MSCT for diagnosis &evaluation of the gastric tumors & followed by histopathological examination for comparison & staging of gastric cancer. According to histopatholgical results we found that out of those 40 patients; 39 patients showed malignant gastric tumors (39/40)(97.5%)&only one patient showed benign gastric neoplasm(2.5%) as shown in [Table 2].
We found that out of 39 patients with malignant gastric tumors; 14 patients with adenocarcinoma (14/39)(35.9%),9 patients with round cell carcinoma (8/39)(20.5%), 7 patients with NHL (7/39)(17.9%) & 5 patients with GISTs (5/39)(12.8%).
All 39 patients with malignant gastric tumors were presented clinically with different complaints(16 patients with dyspepsia,12 patients with vomiting & abdominal pain after meal, 10 patients with dysphagia &obstruction & 5 patients with weight loss &anemia, 2 patients with occult blood in the stool as shown in [Table 3].
|Table 3: Clinical presentation of the 39 patients with malignant gastric tumors of our study|
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Dyspepsia was the most common C/O in the patients with malignant gastric tumors (16/39)(41%) followed by abdominal pain after meal (12/39)(30.8%).
On MSCT of the stomach we found that the cardia & GEJ was the most involved region by a gastric cancer (18/39)(46.2% followed by pyloric canal (6/39)(15.4%) & antrum (5/39)(12.8%) as shown in [Table 4].
|Table 4: MSCT Topographic distribution of the gastric malignant tumors in 39 patients of our study|
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MSCT findings of all 39 patients were recorded & analyzed. We found that out of 39 patients with malignant gastric tumors; 15 patients with circumferential mural thickening (15/39)(38.5%), 10 patients with focal mural thickening (10/39)(25.6%), 9 patients with polypoidal soft tissue mass (9/39)(23.1%)&5 patients with fungating mass (5/39)(12.8%). Also the gastric tumor enhancement were detected in 26 patients (26/39)(66.7%) as shown in [Table 5].
|Table 5: MSCT findings of malignant gastric tumors in the 39 patients of our study|
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Out of 39 patients with malignant gastric tumors;14 patients were proved histopathologically to be T4 (14/39)(35.9%),10 patients as T1 (25.6%), 9 patients as T2 (23.1%) &6 patients as T3(15.4%). MSCT findings of the each patient were recorded, correlated & compared with histopathological results as regards depth of tumor invasion & staging as shown in [Table 6].
|Table 6: Comparison and correlation between MSCT and histopathology as regards tumor depiction and staging in 39 patients of our study|
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Out of 39 patients with malignant gastric tumor; 36 patients were depicted & diagnosed on MSCT also with sensitivity of 92.3%, just only three cases were underestimated as T0 (false –ve). We found that out of 10 patient who had staged histopathologically as T1; 5 patients were staged as T1 on MSCT(50%), 3 patients were underestimated as T0 & another two were overestimated (one as T2 & one as T3). Out of 9patients with T2, 5patients were staged as T2 on MSCT (55.6%), 3 were overestimated as T3 &one was underestimated as T1. Also out of 6 patients with T3, 5 patients were staged as T3 by MSCT, with sensitivity of 83.3% &only one patient was overestimated as T4, while out of 14 patients withT4;12 patients were staged as T4 by MSCT (85.6%) &only two were underestimated as T3.
Also MSCT findings as regard nodal staging &TNM classification were compared & correlated with histopathological findings as shown in [Table 7].
|Table 7: Comparison and correlation between MSCT and histopathology as regards nodal staging and TNM classification in 39 patients of our study|
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We found that out of 30 patients who had staged histopathologically as N0, 25 patients were staged by MSCT as N0, with accuracy (83.3%)& out of 5 patients with N1 staging, only 3 patients were staged as N1 by MSCT(60%), one patient was underestimated as N0 & one was overestimated as N2, while out of 4 patients with N2 staging, 2 patients were staged as T2 on MSCT (50%), the another 2 patients were underestimated (one as N0 & one as N1)..
| Discussion|| |
Gastric cancer is still the second most common cause of cancer-related death in the world . Benign gastric neoplasms are rare conditions, discovered accidentally; the gastric polyp, leiomyoma, and lipoma are the most common benign gastric neoplasms . This coincides with our study, in which, of the 40 patients included in this study, 39 patients were having malignant gastric tumor (39/40) (97.5%) and only one patient had hyperplastic gastric polyp (2.5%).
The role of MDCT is to differentiate between benign and malignant gastric neoplasm and determine the stage and gastric spread of gastric carcinoma, which is vital in choosing between palliative or radical surgical treatment. In addition, MDCT is used to monitor response to treatment. Furthermore, it has been shown to be a very important prognostic factor in patients with gastric cancer by evaluation and estimation of tumor invasion depth after MPR .
In the current study, statistical analysis, correlation, and comparison of MSCT findings with that of histopatholgical results were performed for 39 patients who had malignant gastric tumors. We found that male patients were more affected (22/39) (56.4%) in comparison with female patients (17/39) (43.6%), and the sixth decade group was the most affected age group (17/39). This is in agreement with that the findings of Macdonald et al. , who found that cancer of the stomach affects the male population more commonly compared with the female population. They attributed this to the fact that men are more frequently exposed to the risk factors of gastric cancer.
Most of the patients had complaints at the time of diagnosis in the study of Allum et al. , who found that dyspepsia, dysphagia, weight loss, and anemia were the most common clinical presentation. This coincides with the findings of our study, in which dyspepsia (16/39) (41%) was the most clinical presentation, followed by vomiting with abdominal pain after meal (12/39) (30.8%), dysphagia and obstruction (10/39), and anemia (5/39).
Gastric benign tumors are epithelial (e.g. polyp) and mesenchymal (e.g. lipoma). Gastric adenocarcinoma constitutes more than 95% of malignant tumors of the stomach. The remaining malignant tumors include lymphoma, sarcoma, carcinoid tumors, and metastases . There are different types of gastric cancers: gastric adenocarcinoma, gastrointestinal stromal tumor, gastrointestinal leiomyosacrcoma, and gastrointestinal lymphoma. Adenocarcinoma was the most common type . This coincides with the findings of the current study, in which, of the 39 patients with malignant gastric neoplasm, 14 patients had adenocarcinoma (14/39) (35.9%), nine patients had round cell carcinoma (9/39) (23.1%), seven patients had non-Hodgkin’s lymphoma (7/39) (17.9%), and five patients had gastrointestinal stromal tumor (5/39) (12.8%).
Gastric carcinomas can be classified according to macroscopic appearance. In the early stage, the malignant cells are confined to the mucosa, but with tumor progression the cancer cells invade the outermost layers (submucosa and gastric muscle). In more advanced cases, the malignant cells spread to nearby lymph nodes and eventually to other organs (e.g. pancreas, liver, and colon) ,.
MSCT findings of gastric cancer according to Perez and Brady’s  included focal, nodular, or an irregular thickening of the gastric wall, polypoid soft tissue density, intramural mass, and diffuse mural thickening with narrowing of the lumen. This is in agreement with the findings of our study, in which, of the 39 patients with malignant gastric tumor, 15 patients showed circumferential mural thickening (15/39) (38.5%), 10 patients showed focal irregular mural thickening of the gastric wall (10/39) (25.6%), nine patients revealed polypoidal mass (9/39) (23.1%), and five patients showed fungating soft tissue mass (5/39) (12.8%) with narrowing of the gastric lumen.
In MSCT study, the assessment of gastric wall thickness is an integral part. It was found to vary between 3 and 7 mm. The mucosa of the stomach enhances with intravenous contrast and the stomach layers are best appreciated in the arterial phase of contrast enhancement, when there is no positive contrast in the stomach . Focal thickening of 6 mm or greater in a fully distended stomach and/or focal abnormal enhancement of the gastric wall was considered diagnostic of gastric carcinoma . In our study, gastric tumor enhancement was detected in 26 patients in the arterial phase (26/39) (66.7%) (20 patients with heterogenous and six with homogenous enhancement).
On MSCT, the depth of tumor invasion was classified as follows: T0, no evidence of alteration of the gastric wall with a normal fat plane; T1, invasion to mucosa or submucosa ; T2, invasion to muscularis propria ; T3, invasion to serosa ; and T4, invasion to adjacent organs or structures .
In the current study, the sensitivity of MSCT in depiction and staging of gastric malignant tumors was recorded in comparison and correlation with histopathological results as gold standard. We found that MSCT sensitivity was 85% in T4 staging, 83% in T3, 55% in T2, and 50% in T1 staging. This is in agreement with the results of Yan et al. , who reported that MSCT sensitivity ranged from 68.8 to 96.2% in the detection of gastric cancer.
Regional lymph node were considered to be involved when the shorter axis diameter was greater than 6 mm for the perigastric region, and greater than 8 mm for extraperigastric lymph node. In addition to this size criteria, central necrotic lymph node and clustered lymph node regardless of size were also considered to represent local metastases. N staging was determined as follows: N0, no evidence of lymph node metastasis; N1, one to five lymph nodes; N2, 6–15 lymph nodes; and N3, more than 15 lymph nodes affected ,.
Moreover, the sensitivity of MSCT in staging of nodal metastases was recorded in comparison with histopathological staging by Yan et al. , who reported 72.7% in N0 staging, 82.3% in N1 staging, and 80.7% in N2 staging, whereas in our current study we found that the sensitivity of MSCT was 83.3% in N0 staging, 60% in N1, and 50% in N2 staging.
MSCT is excellent for the detection of distant metastases with gastric cancer as it combines rapid imaging and intravenous contrast with 3D imaging capabilities . Solid organ metastases are uncommon in primary gastric cancers at the time of initial diagnosis, but its detection is important for treatment planning. Hematogenous metastases from gastric carcinoma most commonly involve the liver because the stomach is drained by means of portal vein (PV) . Peritoneal metastases are an extremely unfavorable prognostic factor. The existence of peritoneal metastases implies that the disease is incurable .
Fishman et al.  found that the most common site of metastases in gastric cancer patients is the liver (30.8%) in patients less than 65 years, 66.6% in patients aged more than or equal to 65 years, liver and pancreas (15.4%), the liver and lung(3.8%) in patients aged less than 65 years. In our current study, we found that, of the 39 patients with gastric cancer, 17 patients showed metastases from cancer stomach (17/39) (43.6%); the liver was the most common site of metastases (7/17) (41.2%), followed by peritoneal deposits (4/17) (23.5%), liver and spleen (2/17) (11.8%), and ovary (1/17) (5.9%).
| Conclusion|| |
Recent advances in CT technology imaging software have sparked renewed interest in using CT to evaluate gastric neoplasm.
Detailed CT examination of the stomach can routinely be performed when water is used as an oral contrast agent, along with rapid intravenous contrast bolus and the thin collimation that is possible with new multidetector row CT scanners.
Accurate staging of upper gastrointestinal cancer is essential because surgical resection is the treatment only for localized disease. Endoscopy and conventional barium study can only detect intraluminal lesion, but cannot evaluate extraluminal lesions. Traditional CT can show anatomic structure and gastrointestinal tract lesion but lack continuity.
MSCT has many advantages in the staging of primary tumor, assessing for local spread, and detecting nodal involvement and distant metastases. It can provide valuable additional information and improve the detection and staging of both early and advanced gastric tumors.
MSCT can be the first choice for the preoperative evaluation of patients with gastric carcinoma, with further imaging approaches considered in selected cases.
MSCT in concomitant with continued advancement of the scanners and computer technology may play a future role in the detection of early stage-gastric cancer in high-risk patients and in exact preoperative cancer staging.
MSCT is a valuable tool for detection, staging, surveillance, and post-treatment evaluation of gastric neoplasm.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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