Review Article

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J Innov Med Technol 2023; 1(1): 20-23

Published online November 30, 2023

https://doi.org/10.61940/JIMT.230009

© Korean Innovative Medical Technology Society

Current role of endoscopic ultrasound for the evaluation of pancreatic diseases

Yoon Suk Lee

Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea

Correspondence to : Yoon Suk Lee
Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang 10380, Korea
e-mail lys0326@paik.ac.kr / lys0326@gmail.com
https://orcid.org/0000-0002-5835-9417

Received: November 22, 2023; Accepted: November 22, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

In the advancements of medical technology and endoscopic equipment, endoscopic ultrasonography (EUS) has emerged as a valuable tool, integrating endoscopy and ultrasound functions into a single instrument. EUS offers high-resolution ultrasound images, exceeding those obtained through conventional transabdominal ultrasonography. Furthermore, advanced techniques, such as contrast-enhanced EUS and elastography, have been widely adopted in EUS. Therefore, this paper aims to explore the practical utility of EUS in the evaluation of pancreatic diseases.

Keywords Endosonography; Pancreatic neoplasms; Carcinoma, pancreatic ductal; Pancreatic cyst; Elasticity imaging techniques

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 malignancy10-12. When used in conjunction with EUS, elastography has proven to be highly useful in the differential diagnosis of pancreatic diseases13-15. 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 Săftoiu 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-FNA24,25. 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.

  1. Harinck F, Konings IC, Kluijt I, et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut 2016;65:1505-1513. https://doi.org/10.1136/gutjnl-2014-308008.
    Pubmed CrossRef
  2. Xu MM, Sethi A. Imaging of the pancreas. Gastroenterol Clin North Am 2016;45:101-116. https://doi.org/10.1016/j.gtc.2015.10.010.
    Pubmed CrossRef
  3. Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: a meta-analysis. Gastrointest Endosc 2012;76:301-309. https://doi.org/10.1016/j.gie.2012.02.051.
    Pubmed CrossRef
  4. Saftoiu A, Vilmann P, Bhutani MS. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma. Endosc Ultrasound 2016;5:368-372. https://doi.org/10.4103/2303-9027.190932.
    Pubmed KoreaMed CrossRef
  5. Seicean A, Badea R, Moldovan-Pop A, et al. Harmonic contrast-enhanced endoscopic ultrasonography for the guidance of fine-needle aspiration in solid pancreatic masses. Ultraschall Med 2017;38:174-182. https://doi.org/10.1055/s-0035-1553496.
    Pubmed CrossRef
  6. Gincul R, Palazzo M, Pujol B, et al. Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial. Endoscopy 2014;46:373-379. https://doi.org/10.1055/s-0034-1364969.
    Pubmed CrossRef
  7. Imazu H, Uchiyama Y, Matsunaga K, et al. Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies. Scand J Gastroenterol 2010;45:732-738. https://doi.org/10.3109/00365521003690269.
    Pubmed CrossRef
  8. Piscaglia F, Nolsøe C, Dietrich CF, et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med 2012;33:33-59. https://doi.org/10.1055/s-0031-1281676.
    Pubmed CrossRef
  9. Janssen J, Schlörer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc 2007;65:971-978. https://doi.org/10.1016/j.gie.2006.12.057.
    Pubmed CrossRef
  10. Cochlin DL, Ganatra RH, Griffiths DF. Elastography in the detection of prostatic cancer. Clin Radiol 2002;57:1014-1020. https://doi.org/10.1053/crad.2002.0989.
    Pubmed CrossRef
  11. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008;134:960-974. https://doi.org/10.1053/j.gastro.2008.01.034.
    Pubmed CrossRef
  12. Ophir J, Céspedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging 1991;13:111-134. https://doi.org/10.1177/016173469101300201.
    Pubmed CrossRef
  13. Hirche TO, Ignee A, Barreiros AP, et al. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy 2008;40:910-917. https://doi.org/10.1055/s-2008-1077726.
    Pubmed CrossRef
  14. Săftoiu A, Iordache SA, Gheonea DI, et al. Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc 2010;72:739-747. https://doi.org/10.1016/j.gie.2010.02.056.
    Pubmed CrossRef
  15. Săftoiu A, Vilmann P, Gorunescu F, et al. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy 2011;43:596-603. https://doi.org/10.1055/s-0030-1256314.
    Pubmed CrossRef
  16. Mei M, Ni J, Liu D, Jin P, Sun L. EUS elastography for diagnosis of solid pancreatic masses: a meta-analysis. Gastrointest Endosc 2013;77:578-589. https://doi.org/10.1016/j.gie.2012.09.035.
    Pubmed CrossRef
  17. Săftoiu A, Vilmann P, Gorunescu F, et al. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc 2008;68:1086-1094. https://doi.org/10.1016/j.gie.2008.04.031.
    Pubmed CrossRef
  18. Giovannini M, Hookey LC, Bories E, Pesenti C, Monges G, Delpero JR. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy 2006;38:344-348. Erratum in: Endoscopy 2007;39:257. https://doi.org/10.1055/s-2006-925158.
    Pubmed CrossRef
  19. Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol 2010;105:2079-2084. https://doi.org/10.1038/ajg.2010.122.
    Pubmed CrossRef
  20. Lee YS, Paik KH, Kim HW, Lee JC, Kim J, Hwang JH. Comparison of endoscopic ultrasonography, computed tomography, and magnetic resonance imaging for pancreas cystic lesions. Medicine (Baltimore) 2015;94:e1666. https://doi.org/10.1097/MD.0000000000001666.
    Pubmed KoreaMed CrossRef
  21. Zhang XM, Mitchell DG, Dohke M, Holland GA, Parker L. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 2002;223:547-553. https://doi.org/10.1148/radiol.2232010815.
    Pubmed CrossRef
  22. Enestvedt BK, Ahmad N. To cease or 'de-cyst'? The evaluation and management of pancreatic cystic lesions. Curr Gastroenterol Rep 2013;15:348. https://doi.org/10.1007/s11894-013-0348-y.
    Pubmed CrossRef
  23. Tanaka M, Fernández-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012;12:183-197. https://doi.org/10.1016/j.pan.2012.04.004.
    Pubmed CrossRef
  24. Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:824-848.e22. https://doi.org/10.1053/j.gastro.2015.01.014.
    Pubmed CrossRef
  25. Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819-822; quize812-813. https://doi.org/10.1053/j.gastro.2015.01.015.
    Pubmed CrossRef

Article

Review Article

J Innov Med Technol 2023; 1(1): 20-23

Published online November 30, 2023 https://doi.org/10.61940/JIMT.230009

Copyright © Korean Innovative Medical Technology Society.

Current role of endoscopic ultrasound for the evaluation of pancreatic diseases

Yoon Suk Lee

Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea

Correspondence to:Yoon Suk Lee
Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang 10380, Korea
e-mail lys0326@paik.ac.kr / lys0326@gmail.com
https://orcid.org/0000-0002-5835-9417

Received: November 22, 2023; Accepted: November 22, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In the advancements of medical technology and endoscopic equipment, endoscopic ultrasonography (EUS) has emerged as a valuable tool, integrating endoscopy and ultrasound functions into a single instrument. EUS offers high-resolution ultrasound images, exceeding those obtained through conventional transabdominal ultrasonography. Furthermore, advanced techniques, such as contrast-enhanced EUS and elastography, have been widely adopted in EUS. Therefore, this paper aims to explore the practical utility of EUS in the evaluation of pancreatic diseases.

Keywords: Endosonography, Pancreatic neoplasms, Carcinoma, pancreatic ductal, Pancreatic cyst, Elasticity imaging techniques

Introduction

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.

Differential Diagnosis of Pancreatic Solid Lesions

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 malignancy10-12. When used in conjunction with EUS, elastography has proven to be highly useful in the differential diagnosis of pancreatic diseases13-15. 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 Săftoiu 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.

Differential Diagnosis of Pancreas Cystic Lesions

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-FNA24,25. 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.

Conclusion

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.

Conflict of Interest

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

Funding

None.

Acknowledgments

None.

References

  1. Harinck F, Konings IC, Kluijt I, et al. A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals. Gut 2016;65:1505-1513. https://doi.org/10.1136/gutjnl-2014-308008.
    Pubmed CrossRef
  2. Xu MM, Sethi A. Imaging of the pancreas. Gastroenterol Clin North Am 2016;45:101-116. https://doi.org/10.1016/j.gtc.2015.10.010.
    Pubmed CrossRef
  3. Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: a meta-analysis. Gastrointest Endosc 2012;76:301-309. https://doi.org/10.1016/j.gie.2012.02.051.
    Pubmed CrossRef
  4. Saftoiu A, Vilmann P, Bhutani MS. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma. Endosc Ultrasound 2016;5:368-372. https://doi.org/10.4103/2303-9027.190932.
    Pubmed KoreaMed CrossRef
  5. Seicean A, Badea R, Moldovan-Pop A, et al. Harmonic contrast-enhanced endoscopic ultrasonography for the guidance of fine-needle aspiration in solid pancreatic masses. Ultraschall Med 2017;38:174-182. https://doi.org/10.1055/s-0035-1553496.
    Pubmed CrossRef
  6. Gincul R, Palazzo M, Pujol B, et al. Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial. Endoscopy 2014;46:373-379. https://doi.org/10.1055/s-0034-1364969.
    Pubmed CrossRef
  7. Imazu H, Uchiyama Y, Matsunaga K, et al. Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies. Scand J Gastroenterol 2010;45:732-738. https://doi.org/10.3109/00365521003690269.
    Pubmed CrossRef
  8. Piscaglia F, Nolsøe C, Dietrich CF, et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med 2012;33:33-59. https://doi.org/10.1055/s-0031-1281676.
    Pubmed CrossRef
  9. Janssen J, Schlörer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc 2007;65:971-978. https://doi.org/10.1016/j.gie.2006.12.057.
    Pubmed CrossRef
  10. Cochlin DL, Ganatra RH, Griffiths DF. Elastography in the detection of prostatic cancer. Clin Radiol 2002;57:1014-1020. https://doi.org/10.1053/crad.2002.0989.
    Pubmed CrossRef
  11. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008;134:960-974. https://doi.org/10.1053/j.gastro.2008.01.034.
    Pubmed CrossRef
  12. Ophir J, Céspedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging 1991;13:111-134. https://doi.org/10.1177/016173469101300201.
    Pubmed CrossRef
  13. Hirche TO, Ignee A, Barreiros AP, et al. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy 2008;40:910-917. https://doi.org/10.1055/s-2008-1077726.
    Pubmed CrossRef
  14. Săftoiu A, Iordache SA, Gheonea DI, et al. Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc 2010;72:739-747. https://doi.org/10.1016/j.gie.2010.02.056.
    Pubmed CrossRef
  15. Săftoiu A, Vilmann P, Gorunescu F, et al. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy 2011;43:596-603. https://doi.org/10.1055/s-0030-1256314.
    Pubmed CrossRef
  16. Mei M, Ni J, Liu D, Jin P, Sun L. EUS elastography for diagnosis of solid pancreatic masses: a meta-analysis. Gastrointest Endosc 2013;77:578-589. https://doi.org/10.1016/j.gie.2012.09.035.
    Pubmed CrossRef
  17. Săftoiu A, Vilmann P, Gorunescu F, et al. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc 2008;68:1086-1094. https://doi.org/10.1016/j.gie.2008.04.031.
    Pubmed CrossRef
  18. Giovannini M, Hookey LC, Bories E, Pesenti C, Monges G, Delpero JR. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy 2006;38:344-348. Erratum in: Endoscopy 2007;39:257. https://doi.org/10.1055/s-2006-925158.
    Pubmed CrossRef
  19. Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol 2010;105:2079-2084. https://doi.org/10.1038/ajg.2010.122.
    Pubmed CrossRef
  20. Lee YS, Paik KH, Kim HW, Lee JC, Kim J, Hwang JH. Comparison of endoscopic ultrasonography, computed tomography, and magnetic resonance imaging for pancreas cystic lesions. Medicine (Baltimore) 2015;94:e1666. https://doi.org/10.1097/MD.0000000000001666.
    Pubmed KoreaMed CrossRef
  21. Zhang XM, Mitchell DG, Dohke M, Holland GA, Parker L. Pancreatic cysts: depiction on single-shot fast spin-echo MR images. Radiology 2002;223:547-553. https://doi.org/10.1148/radiol.2232010815.
    Pubmed CrossRef
  22. Enestvedt BK, Ahmad N. To cease or 'de-cyst'? The evaluation and management of pancreatic cystic lesions. Curr Gastroenterol Rep 2013;15:348. https://doi.org/10.1007/s11894-013-0348-y.
    Pubmed CrossRef
  23. Tanaka M, Fernández-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012;12:183-197. https://doi.org/10.1016/j.pan.2012.04.004.
    Pubmed CrossRef
  24. Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:824-848.e22. https://doi.org/10.1053/j.gastro.2015.01.014.
    Pubmed CrossRef
  25. Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819-822; quize812-813. https://doi.org/10.1053/j.gastro.2015.01.015.
    Pubmed CrossRef
Journal of Innovative Medical Technology
Nov 30, 2023 Vol.1 No.1, pp. 1~9

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