The American Gastroenterological Association guidelines4 have indicated that the risk of malignancy of PCLs in asymptomatic patients is significantly increased in patients with a cyst >3 cm, in patients with a solid component, and in patients with a dilated duct. Nevertheless, this guideline does not include symptomatic patients with PCLs or patients with SPNs and NENs. Asymptomatic patients with small (<1 cm) PCNs also need a diagnostic work-up because malignancy can also occur (2%).6 As a consequence, the timely distinguishing PCNs from nonneoplastic PCLs and accurate diagnosis of these patients are also of importance to help clinical management. As a consequence, we use “cyst size”, “nodule”, “septa”, and “duct dilatation” as research indicators. It should be noted that “septa” is an indicator to help discriminate between neoplastic and nonneoplastic cysts, SCA and MCA.22
The accepted first-line imaging modalities for PCN surveillance are CT and MRI, and the Korean Society of Abdominal Radiology recommends that both contrast-enhanced MRI with MRCP and contrast-enhanced CT with multiplanar reformation be used as imaging modalities for the follow-up of incidental pancreatic cystic lesions. However, some cystic lesions display similar morphologic characteristics, complicating the differentiation of neoplastic from nonneoplastic PCLs.4
In our study, MRI was determined to be the best diagnostic imaging modality for these patients, outperforming CEUS and CT. However, CEUS showed no significant diagnostic differences with MRI in whether discriminating PCNs from nonneoplastic PCLs or differentiating the specific type of PCN. In characterizing the specific type of PCNs, MRI and CEUS both excel in CT. A previous study reported that the accuracy of CT and MRI in making the correct diagnosis for PCLs ranges from 40% to 60%,23–25 which is lower than that reported herein. Fan et al12 reported that CEUS showed substantial agreement with enhanced CT for the diagnostic classification accuracy of pancreatic cystic lesions. In this study, although the ultrasound physician was blinded to the CT and MRI results, it is difficult to avoid receiving related information from the patient or their relatives. This may have led to the higher diagnostic performance observed for CEUS.
For evaluating the size and detection of duct dilatation, there were no significant differences among CEUS, MRI and CT. This finding suggests that if we follow-up changes in size or duct dilatation, these imaging methods have the same value. Nevertheless, when these lesions were bounded by 3 cm, CEUS had a relatively poor diagnostic performance in group<3 cm, which actually comprised6 cysts smaller than 2 cm and 14 located in the unicate or tail. For patients with small cystic pancreatic lesions smaller than 2 cm, it is sometimes difficult to judge the inner structure, especially when these lesions are located in the unicate or tail where the presence of gastrointestinal gas can obscure imaging.
The septa and nodule detection rates by CEUS in our research were both much higher than those by CT and MRI, especially good at the nodule detection ability. Previously, M. D’Onofrio et al20 reported that the difference between the diagnostic accuracy of CEUS and that of MRI was not significant in the identification of septa and nodules. Septa and nodules were always observed more clearly on T2-weighted MRI images than on contrast-enhanced MRI images (Figures 2 and 3). These inner structures are more difficult to detect on plain CT images, so their identification is mainly depend on contrast-enhanced CT (Figure 2). The slice thickness or artifacts from the breathing movement may have led to missed diagnosis on CT or MRI. During contrast-enhanced sonography, due to its real-time dynamic properties, it is easy to visualize these structures as the contrast agent passes into the capillary beds of the septa (Figures 2 and 3) or nodule (Figure 3) inside the lesion.12,20,21 This finding explains the larger number of detections of these inner structures on CEUS than on CT or MRI in our study. The ability to detect septa and nodules can contribute to the differentiation of a cystic neoplasm from a nonneoplasm, as well as the determination of their possible malignant potential.20,26
As the most common types of PCNs, SCAs and MCAs have adverse biological behaviors. Therefore, the ability to differentiate SCAs from MCAs is important. In agreement with our previous study,22 there was a significant difference in the shape and number of septa in discriminating these two adenomas, but the statistics of “location” were inconsistent with our previous results, mainly because of the two different samples used. SCAs were originally identified as “microcystic adenomas”, but this classification has been criticized soon on account of reports of macrocystic variants, which are similar to the main type of MCAs.27 In our study, there were 14 oligocyst SCAs with regular morphology and 9 had no septa.
In the western hemisphere, SCNs account for 32% to 39%, MCNs for 10% to 45%, IPMNs for 21% to 33%, and SPNs for less than 10% of all PCNs.4,6 Nevertheless, IPMNs accounted for only 12.2% (11/90) in our cohort. The relatively low prevalence of IPMNs may be due to the following two aspects. First, unlike SCAs and MCNs, IPMNs are found in older individuals between 60 and 70 years of age.28 In our study, we included only patients with a median age of 42.6 (18–71) years who underwent surgery. Some elderly individuals who were unwilling or unsuitable for surgical treatment might cause a lack of IPMNs. Second, patients with acute pancreatitis were excluded from this work; however, it was reported that the typical symptoms of IPMNs include abdominal pain (55%), weight loss (45%), jaundice (17%), and acute pancreatitis (15%).28
Notably, some of the patients in this study underwent EUS with or without FNA. As mentioned in some articles and guidelines,4,6,28-30 if the results of the traditional technique indicate nondiagnostic or “suspicious” morphological aspects, EUS with or without FNA is recommended, which is valuable for the differential diagnosis and prediction of the malignancy of pancreatic cysts. However, as EUS is an invasive examination that poses greater risk and may also not be readily available in some hospitals, we compared only these traditional imaging modalities in our study. Moreover, the role of FNA is still limited, especially in discriminating IPMN from MCA;31 therefore, surgical pathology is regarded as the diagnostic standard.
There were several limitations to this study. First, there was a high sensitivity for discriminating PCN from nonneoplastic PCL probability because the enrolled patients were all pathologically diagnosed with PCNs, and the lesions clinically diagnosed with nonneoplasms, mainly pseudocysts, were mostly suggested to occur during follow-up. Second, CEUS is highly operator dependent, and the ultrasound physicians were both experienced in CEUS, particularly in PCNs, which could have had affected the final diagnosis. Third, the detection of septa and nodules has not been completely correlated with the anatomic appearance of the specimens, which could lead to subjective evaluations. Last, as this is a prospective study, a pilot study was conducted for measuring the diagnostic capacity of these three imaging modalities to estimate the group size. According to the statistical formula, we needed 100 patients to evaluate the diagnostic capacity of CEUS, 109 patients for CT and 92 patients for MRI, so an additional study in a larger population is needed.
Altogether, the results of our study suggest that, as an economic, radiation-free, and effective imaging modality, CEUS can be used as an optional examination method and contribute to the diagnosis and classification of PCNs.
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