JIMT

With advancements in medical technology and equipment for endoscopy, endoscopic ultrasonography (EUS) has been developed with integrating the function of endoscopy and ultrasound into a single instrument. In comparison to endoscopic retrograde cholangiopancreatography (ERCP), EUS is a relatively safe method and offers the advantage of obtaining high-resolution ultrasound images compared to conventional transabdominal ultrasonography. Recently, the indications of EUS examinations have been expanded and widely utilized for the evaluation of pancreatic diseases; EUS is not only used for diagnostic purposes but also increasingly for therapeutic interventions. The pancreatic images observed in EUS closely resemble those obtained with conventional transabdominal ultrasound. However, due to its higher frequency and the ability to avoid interference from intraluminal gases, EUS enables a detailed visualization of pancreatic images without significant blind spots compared to conventional abdominal ultrasound. Many reports suggest that it can serve as a substitute for ERCP and radiologic interventions. Therefore, this paper aims to explore the utility of EUS in evaluating pancreatic diseases.

The sensitivity of EUS in the diagnosis of pancreatic masses is reported to be very high, ranging from 91% to 98%, making it superior to computed tomography (CT) with a sensitivity of 63% to 92% and ultrasonography with a sensitivity of 67% to 91%. However, the superiority between EUS and magnetic resonance imaging (MRI) is not yet clear, and there are limited prospective studies comparing the two modalities. In a recent multicenter prospective study conducted by Harinck et al.¹ in 2016, the diagnostic abilities of EUS and MRI for pancreatic lesions were compared. A total of 139 patients with high-risk factors for pancreatic cancer were enrolled, and both EUS and MRI were performed to compare the detection rates of clinically significant pancreatic lesions. EUS demonstrated higher sensitivity in detecting solid lesions of the pancreas, while MRI was more sensitive in detecting cystic lesions. The authors concluded that rather than one being superior to the other, the two modalities complement each other. However, it’s noteworthy that two solid pancreatic lesions observed on EUS were not detected by MRI, and surgical findings confirmed pancreatic cancer and pancreas intraepithelial neoplasia (PanIN) grade III¹. Therefore, for small solid tumors in the pancreas, EUS may be a more sensitive method compared to MRI.

In the case of pancreatic cancer, it is usually observed as a hypoechoic mass with indistinct or irregular tumor margins and heterogeneous echotextures of the mass. Additionally, cystic degeneration due to tumor necrosis may result in non-echoic lesions, and when accompanied by calcifications, they appear hyperechoic². Smaller pancreatic cancers (≤3 cm) tend to exhibit more homogeneity and smooth contours, while larger tumors show increased inhomogeneity, with frequencies of necrosis and calcifications higher as the tumor size increases. In very large tumors, ultrasound penetration may be compromised, making it challenging to clearly distinguish the main lesion and its boundaries. Pancreatic duct dilation in the upstream portion and expansion of the main pancreatic duct due to compression or invasion in pancreatic head cancer are often concurrent findings. Of course, there are limitations to EUS examinations as well. Particularly, anatomical changes resulting from previous surgeries can make observing the pancreatic head difficult, and in patients with concomitant chronic pancreatitis, distinguishing between the surrounding pancreatic parenchyma and masses can be challenging. Observation may also be difficult in the ventral and dorsal split areas of the pancreas, in cases where drainage tubes are inserted into the bile duct and pancreatic duct, and in the presence of severe inflammation due to acute pancreatitis. Moreover, autoimmune pancreatitis can mimic pancreatic masses, making it challenging to differentiate from pancreatic cancer using conventional EUS alone. Recently, to overcome the limitations of conventional EUS, elastography and contrast-enhanced EUS (CE-EUS) techniques have been devised and extensively researched. These advancements are expected to address the shortcomings of conventional EUS and improve diagnostic accuracy.

Contrast-enhanced EUS

CE-EUS is a diagnostic technique by using the contrast agent. In addition to conventional ultrasound imaging of EUS, it provides the contrast enhancement pattern of lesions similar to contrast-enhanced CT. Therefore, it allows for the assessment of microvascular distribution and vascular perfusion status, contributing to an improved diagnostic accuracy when performed alongside conventional endoscopic ultrasound. According to a meta-analysis by Gong et al.³ in 2012, CE-EUS demonstrated a sensitivity of 94%, specificity of 89%, and an area under the receiver operating characteristic curve of 0.9732, indicating a highly accurate diagnostic performance. The distinctive contrast enhancement patterns aid in differentiation between various pancreas diseases. For instance, mass-forming pancreatitis and pancreatic neuroendocrine tumors may exhibit an iso- or hyper-enhanced pattern, while pancreatic cancer often presents with a hypo-enhanced pattern⁴.

Recently, as the introduction of harmonic imaging techniques and the development of microbubble contrast agents, have enabled more detailed CE-EUS⁵. According to the study from Gincul et al.⁶, even if EUS-fine needle aspiration (FNA) yields a negative result, the absence of contrast enhancement in CE-EUS can still lead to a diagnosis of pancreatic cancer. Furthermore, targeting areas with confirmed contrast enhancement in lesions during EUS-FNA has been shown to increase the accuracy of the procedure⁵. This targeted approach not only enhances diagnostic accuracy but also facilitates clearer delineation of surrounding vessels during staging, contributing to more precise decisions regarding the need for surgery⁷.

The methodology for performing CE-EUS is detailed in the guidelines and recommendations of EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology)⁸. Additionally, software has been developed to quantitatively analyze these contrast enhancement patterns, allowing for a more objective and discerning diagnosis of lesions.

EUS elastography

Elastography is a diagnostic technique that measures the relative tissue stiffness between solid lesions and surrounding tissues⁹. It is widely used in breast ultrasound, prostate ultrasound, thyroid ultrasound, and for measuring fibrosis in the liver. By generating low-frequency elastic waves from a probe, the speed of propagation and reflection of ultrasound through the lesion is measured. This information is then integrated into B-mode gray-scale scans and displayed with color differentiation. Generally, higher tissue elasticity is associated with a higher likelihood of malignancy^10-12. When used in conjunction with EUS, elastography has proven to be highly useful in the differential diagnosis of pancreatic diseases^13-15. According to recent meta-analyses, EUS elastography demonstrates a high reliability, with sensitivity ranging from 95% to 97% and specificity from 67% to 76% in distinguishing pancreatic solid lesions¹⁶. Additionally, when combined with EUS-FNA, which has high specificity but lower sensitivity (approximately 75%), the accuracy of the diagnosis is further improved. A Study by S^ăftoiu et al.¹⁷, suggest that if elastography shows a green-predominant pattern when cytology results from FNA are negative, there is a high likelihood of a true negative result. Conversely, if a blue-predominant elastography pattern is observed, negative cytology is more likely to be a false negative, warranting additional FNA¹⁷. Furthermore, EUS elastography can assist in selecting the optimal location for FNA, enhancing diagnostic accuracy¹⁸. Despite its limitations, including potential variability among observers and the requirement for proximity to the probe due to the use of high frequencies, EUS elastography is a promising diagnostic tool when used in conjunction with conventional EUS. Ongoing research and high expectations surround this method, given the additional information it can provide.

Due to the widespread availability of health screenings and advancements in imaging devices, there has been an increase in the incidental discovery of pancreatic cystic lesions. The prevalence of these lesions has been reported to range from as low as 2.5% to as high as 19.8%^19-21. Pancreatic cystic lesions are categorized into neoplastic and non-neoplastic lesions. Among neoplastic lesions, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) are known for their potential for malignant transformation²². Therefore, risk stratification and ongoing surveillance for the risk of malignancy in these lesions, pose crucial challenges in clinical practice.

For cystic lesions measuring less than 1 cm without main pancreatic duct dilation that the likelihood of being a branch duct type IPMN is high and the risk of malignancy is low, additional EUS may not be necessary. However, for cystic lesions larger than 3 cm, especially those associated with macrocystic serous cystic neoplasms (SCN) or mucin-producing neoplasms including MCN and IPMN, aspirating cystic fluid for analysis can aid in distinguishing between them. EUS can be performed to assess the presence of nodules, predict the risk of malignancy through cytology, and aid in the differentiation of macrocystic SCN and MCN.

According to the 2012 Fukuoka guidelines²³, high-risk stigmata for malignant transformation include the presence of a cystic lesion in the pancreatic head with concurrent obstructive jaundice, enhancing solid components within the cyst, and main pancreatic duct dilation of ≥10 mm. In such cases, proactive surgical intervention is recommended. Additionally, 'worrisome features' clinically refer to pancreatic cystic lesions associated with pancreatitis and, radiologically, are defined by five criteria: cyst size ≥3 cm, thickened/enhancing cyst walls, main pancreatic duct dilation of 5–9 mm, non-enhancing mural nodule, and abrupt change in caliber of pancreatic duct with distal pancreatic atrophy. The presence of these features suggests the need for EUS examination.

However, in 2015, the American Gastroenterological Association Institute introduced new guidelines for asymptomatic pancreatic cystic lesions, emphasizing the role of EUS-FNA^24,25. They recommend EUS-FNA if two or more of the following criteria are present: cyst size ≥3 cm, dilated main pancreatic duct, or the presence of an associated solid component. The guidelines also specify criteria for discontinuing surveillance, recommending cessation after five years if no significant changes are observed or if the patient is not a surgical candidate due to increased surgical risks.

EUS examinations have seen a broadening and diversification of applications due to significant advancements in equipment and technology. Recent developments such as CE-EUS and EUS elastography, in addition to the widespread use of FNA and advancements in interventional procedures, have enhanced the diagnostic capabilities of conventional EUS examinations. The role of EUS in pancreatic diseases is expected to continue expanding. Therefore, when encountering pancreatic diseases, it is crucial to consider not only CT and MRI but also EUS for diagnosis and treatment. Familiarizing oneself with disease specific EUS findings, understanding the strengths and limitations of the procedure, and interpreting results clearly will be important tasks for determining appropriate follow-up observations and treatment plans in the future.

No potential conflict of interest relevant to this article was reported.

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