1. Introduction
Pancreatic carcinoma is one of leading causes of cancer death and increasing in incidence. Despite advances in diagnosing modalities, most patients with pancreatic cancer are still unresectable at the time of diagnosis. Surgery remains the only potential for long-term survival, with a resectability rate of around 15% - 20% in the latest review [1]. Even in patients with resectable disease, the 5-year survival rate is still around 20% [1-3]. Clearly, an effort has to be made for diagnosing early stage cancer, also by determining its clinical stage and by accurately predicting the prognosis.
However, diagnosis, clinical staging and treatment of pancreatic carcinoma remain difficult. Suspicions of pancreatic cancer are often raised by sonography or CT findings, including the presence of a low-attenuation pancreatic mass and dilatation of the pancreatic duct or biliary tree (to both). CT is the most common diagnostic imaging modality used in the preoperative diagnosis of pancreatic cancer. This technique can also access vascular involvement and invasion of adjacent organs. Unfortunately, interpretation of CT is sometimes difficult in mass-forming pancreatitis or in questionable findings.
The advantages of positron emission tomography using 18F-fluorodeoxyglucose (18F-FDG) on diagnosing pancreatic cancer, especially small lesions less than 2 cm in size, over the conventional modalities, including computed tomography (CT), have been reported [2]. Furthermore, 18F-FDG PET has also been reported to possibly play a role in predicting the prognosis of pancreatic cancer [2,4-6].
However, a limiting factor for the sensitivity of PET is the limited resolution of the method and the specificity is the difficulty to differ malignant diseases from pancreatitis. By the use of fusion systems combining PET and CT, diagnose may be improved, even though assessment of vascular invasion is still difficult. In this article, we compare the use of non-enhanced PET/CT and enhanced PET/CT on pancreatic tumor and suggested combining use of PET and enhanced CT to improve diagnosing accuracy.
2. Materials and Methods
2.1. Patient Population
Among seventeen patients with benign diseases, five patients underwent surgery and twelve patients underwent conservative therapy. Seven patients deemed surgical candidates were changed to non-surgical treatment because enhanced PET/CT exams found bone, lung, or liver distant metastases and organ infiltration. Bone, liver distant metastases and organ infiltration were confirmed by pathology, and lung metastases were confirmed by clinical follow up. All patients performed 6-mo follow-up period after examination.
2.2. PET/CT Imaging
18F-FDG PET/CT exams were performed with a GE Discovery STE16 PET/CT (General Electric Medical systems). Patients were required to fast for at least 4 h before PET scanning and serum glucose level was controlled under the level of 7.4 mmol/L. Approximately 60 min after the intravenous administration of 18F-FDG 0.12 - 0.15 mCi/kg, PET/CT scan was acquired.
Initially, CT scan was acquired starting from the level of the head to the thigh using the following parameters: 120 - 180 mAs, 140 kV, a gantry rotation, a slice thickness of 3.75 mm. The CT scan was acquired during breath holding in the normal expiratory position. The low dose CT data were used for attenuation correction and lesion localization, and the images were reconstructed using a standard iterative algorithm. Immediately after the CT acquisition, a PET scan was acquired.
Six to seven bed positions that included the head to the thigh were imaged. Emission images were acquired for 3 min per bed position. The axial field of view of this system is 15.6 cm. Integrated PET and CT images were obtained automatically on Xeleris (GE Healthcare) or Advantage workstations (GE Healthcare).
The acquired images were reviewed with software providing multi-planar reformatted images of PET alone, CT alone, and fused non-enhanced PET/CT and enhanced CT images with linked cursors using a Xeleris workstation (GE Healthcare).
Clinical information was used in addition to CT scans for localization of the pancreatic head to differentiate between abnormal uptake in the head of the pancreas and physiologic uptake in an adjacent loop of bowel. Visual analysis was performed using background liver uptake as a reference (uptake greater than liver background corresponding to the head of the pancreas on CT was considered malignant). The attenuation-corrected images were analyzed semi-quantitatively, using the SUVs by the physician who performed the visual interpretation. The SUV was calculated as: SUV = (activity in region of interest in mCi/mL)/(injected dose in mCi/weight in kg).
2.3. Enhanced CT Imaging
Afterward, enhanced CT scans of the abdomen were obtained with 5-mm collimation and a table speed of 5 mm/s (pitch 1 or 2) and 20 - 25 s after intravenous contrast administration (150 mL, Ultravist, at a rate of 3 mL/s) and then again 60 - 70 s during the portal phase. The images were reconstructed with 3.75 - 5 mm thicknesses.
Forty-two patients presented with PET/CT and enhanced CT of the abdomen performed at our hospital at the same time. Fourteen patients performed enhanced CT at outside institutions and these studies were not repeated because intravenous contrast was identified in the superior mesenteric vein, and pancreatic parenchyma enhancement was present. The time duration between the PET/CT and enhanced CT was no more than one week.
2.4. Image Interpretation
The PET/CT images were analyzed by 2 dual-boardcertified nuclear radiology physicians. Images were evaluated by consensus. First, the reader interpreted the PET images alone; in a second step, the reader interpreted the non-enhanced PET/CT images; and in a third step, the reader interpreted the enhanced PET/CT images. The PET images were analyzed for the presence and nature of lesions with focally increased 18F-FDG uptake. For all patients, the attenuation-corrected PET images were used for analysis. Lesions were interpreted as metastases if the uptake was higher than the uptake of the surrounding background tissue so that a focal lesion was clearly depicted. The enhanced-CT part was analyzed using the established criteria for the assessment of the primary tumor: vessel involvement, organ infiltration, and distant metastases.
2.5. Statistical Analysis
The chi-square test was employed for a statistical comparison of the sensitivity of 18F-FDG PET and CT. The Student’s test was used to compare the values of the SUVmax between the two groups. Correlations between the SUVmax with the maximum diameter of the lesion, distant metastases, and survival time were examined by the Pearson’s correlation test. Correlation between distant metastases with survival time was tested by the Pearson’s correlation test. Survival functions of two groups were analyzed by using Log-Rank test. All statistical analyses were performed using the SPSS software program (SPSS 13.0). A P value < 0.05 was considered statistically significant.
3. Results
3.1. Sensitivity for Diagnosing Pancreatic Disease
A total of 56 patients underwent both 18F-FDG PET/CT imaging and CT enhancement scanning for the diagnosis of suspected primary pancreatic adenocarcinoma during the study period. The distribution of patients is summarized in Table 1. Among these 56 patients, 39 malignant diseases and 17 benign lesions were identified. Among the 39 patients with pancreatic malignant diseases, maximum tumor diameter was measured by CT. Tumor size ranged from 0.5 cm to 5.6 cm.
Sensitivity, specificity and accuracy of enhanced CT were 87.5%, 75.0% and 83.9%, those of non-enhanced PET/CT were 89.7%, 88.2% and 89.2%, of PET/CT with enhanced CT were 100%, 94.1% and 98.2%. Combined PET/CT with enhanced CT had highest sensitivity, specificity and accuracy in diagnosing pancreatic carcinoma (Table 2).
Four false negative and two false positive PET/CT (SUVmax 2.5 as standard) scans were found. There were two reasons to select SUVmax 2.5 as standard. First reason to select SUVmax 2.5 is according to references [3-7]. Second we compared diagnosis accuracy of PET (SUVmax 2.0, 2.5, 3.0, respectively) and diagnosis accuracy with SUVmax 2.5 was highest. So, we select SUVmax 2.5 as standard. And there were four falsepositive and five false-negative in enhanced CT scans, which was correctly diagnosed by PET/CT. Combined PET/CT with enhanced CT, hybrid approach correctly diagnosed 55 cases finally. Accuracy of hybrid diagnose means is 98.2% higher than other single means.
3.2. Distribution of SUVmax
The distribution of SUVmax in benign and malignant pancreatic lesion is shown in Figure 1. The SUVmax of the patients with pancreatic adenocarcinoma ranged from 1.7 to 18.9 and that of benign disease ranged from 1.2 to 5.0. Overall mean SUVmax for patients with malignant disease was 6.72 ± 3.84, compared with 2.56 ± 1.22 for patients with benign disease. This difference was statistically significant (P < 0.05).
Figure 1. Distribution of standardized uptake values (SUVmax) for benign and malignant pancreatic lesions.
Table 1. Distribution of patient population (n = 56).
Table 2. Value of enhanced CT, PET/CT, PET/CT+ enhanced CT.
Among pancreatic malignant diseases, four failed to highly uptake 18F-FDG with SUVmax of 1.7, 2.1, 2.3, and 2.4. Five patients with pancreatitis showed high 18F-FDG uptake with SUV of 3.1, 3.5, 3.7, 4.5 and 5.0. An example of false negative PET/CT imaging for pancreatic cancer is presented in Figure 2.
Some benign inflammatory lesions accumulated 18FFDG and result in false-positive interpretations on PET images as Figure 3 showed.
3.3. Relationship between SUV and Lesion Size
Figure 4 showed correlation between the SUVmax and the maximum diameter of the primary lesion measured on CT by using Pearson’s correlation test (Pearson = 0.416, P < 0.01). Figure 4 also showed there were two patients had malignant lesions with diameter smaller than 2 cm among the three false-negative PET/CT examinations. Small lesions that suffer from partial volume averaging can lead to false-negative interpretation.