Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
doi: 10.1111/den.12444
Clinical evaluation of new diagnostic modalities of EUS for pancreatobiliary diseases
Clinical evaluation of new diagnostic modalities of endoscopic ultrasound for pancreaticobiliary diseases Anthony Yuen Bun Teoh1 and Raymond Shing Yan Tang2 1
Department of Surgery, Prince of Wales Hospital and 2Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Endoscopic ultrasonography (EUS) is currently an integral tool for work-up of pancreaticobiliary neoplasms. Tissue acquisition by EUS is possible with fine-needle aspiration (FNA) cytology and histology. However, FNA still carries some limitations and risks of complications. The use of image-enhanced EUS may improve detection and characterization of pancreaticobiliary neoplasms and complement FNA. The present article aims to provide an
INTRODUCTION
E
NDOSCOPIC ULTRASONOGRAPHY (EUS) is currently an important tool for the diagnosis of pancreaticobiliary diseases. The modality has the capability of obtaining fine-needle aspiration (FNA) cytology and histology. However, FNA still carries some limitations and risks of complications. Recently, improvements in EUS hardware and programming have provided new options for imageenhanced EUS that may improve detection and characterization of pancreaticobiliary neoplasms. The present article aims to provide an overview of the current development of contrast-enhanced imaging and elastography in EUS and their potential application in the diagnosis of pancreaticobiliary diseases.
WHY DO WE NEED IMAGE ENHANCEMENT IN EUS?
U
LTRASONOGRAPHY IS ONE of the earliest diagnostic modalities used for medical imaging. The technology detects the reflection of high-frequency mechanical sound energy from the target organ to produce gray-scale
bs_bs_banner
Corresponding: Anthony Yuen Bun Teoh, Department of Surgery, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. Email: [email protected] This manuscript is being submitted as an Invited review article for Digestive Endoscopy. Received 17 December 2014; accepted 19 January 2015.
overview of the current development of contrast-enhanced imaging and elastography in EUS and their potential application in the diagnosis of pancreaticobiliary diseases. Key words: contrast-enhanced endoscopic ultrasonography, elastography, image enhanced endoscopic ultrasonography, tissue harmonic imaging
images over a 2D plane.1 The combination of endoscopy and ultrasonography has revolutionized pancreaticobiliary tract imaging; however, EUS still suffers from limitations common to ultrasound technology including inadequate characterization, operator dependency and limited penetration. Tissue acquisition through FNA may help overcome some of these limitations but FNA is associated with risk of needle-track seeding, false negativity, and the procedure may not be desirable in some situations. Recently, improvements in EUS hardware and programming have provided new options for image enhancement during EUS. Contrast-enhancement and elastography are novel modalities that may improve detection and characterization of suspicious lesions. Contrast-enhancement allows characterization of the microvasculature of lesions whereas elastography depicts the stiffness of lesions.2,3 Furthermore, quantitative measurements are possible and this provides nominal assessments of the lesions and may reduce interobserver disagreement.
EUS-ELASTOGRAPHY
G
IOVANNINI ET AL. FIRST described elastography for EUS in 2006.2 The basis of the technology is that many different pathological processes, including inflammation, fibrosis, and cancer, induce alterations in tissue stiffness. The elastic properties of tissues are measured by applying small amounts of stress causing axial displacement of tissues. Pre- and post-compression images are then compared to produce a measurement of strain and real-time display of an
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
55
56
A. Y. B. Teoh and R. S. Y. Tang
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
Table 1 Classification of elastography findings on pancreatic masses Score
Elastography findings
Pathology
1
Homogeneous hypoechoic area (soft, green) Heterogeneous but soft tissue range (green, yellow and red) Largely blue with minimal heterogeneity Hypoechoic central region with a green center surrounded by blue tissue Heterogeneous lesions largely blue but mixed with softer tissue colors (green, red)
Normal pancreatic tissue Fibrosis
2
3 4
5
Small early pancreatic adenocarcinoma Neuroendocrine tumor or pancreatic metastasis Advanced pancreatic adenocarcinoma with necrosis
elastogram. This allows measurement of the ‘hardness’ of the tissue and differentiation between benign (soft) and malignant (hard) tissues. Elastography images can be obtained by both radial and linear echoendoscopes. The region of interest under examination should contain approximately 50% lesion and 50% normal/surrounding tissue to allow for comparison.4 In addition, the effectiveness of elastography in determining the nature of the lesion depends significantly on the types of differential diagnosis under consideration and it is different for each organ or structure.
Elastography in differentiating pancreatic masses The main differential diagnoses in assessing pancreatic masses include pancreatic adenocarcinoma, fibrosis from chronic pancreatitis or neuroendocrine tumor (PNET). In an aim to classify elastography images of each of these conditions, an elastic scoring system was derived (Table 1; Fig. 1).2 With this classification, elastography images of 24 pancreatic masses were evaluated and a sensitivity of 100% and specificity 67% were obtained. Thereafter, multiple studies have assessed the usefulness of elastography in differentiating between normal pancreas, chronic pancreatitis and pancreatic adenocarcinoma and the results from two meta-analyses are available.5,6 In the first meta-analysis, 10 studies including 893 pancreatic masses were analyzed.5 The pooled sensitivity and specificity were 0.98 (95% confidence interval [CI] 0.93–1.00) and 0.69 (95% CI 0.52–0.82) respectively. Results from qualitative and quantitative EUS elastography were similar. The area under receiver operator characteristic (ROC) curve was 0.94. In the other metaanalysis, 1044 patients from 13 studies were included.6 The pooled sensitivity and specificity were 0.95 (95% CI 0.94–
Figure 1 Elastography assessment of pancreatic adenocarcinoma showing a hard lesion.
0.97) and 0.67 (95% CI 0.61–0.73) and the area under ROC curve was 0.9046. These studies concluded that elastography is a reliable tool for characterization of pancreatic mass and complementary to FNA. However, the main drawback was the moderate specificity. This was attributable to the difficulty in differentiating fibrosis seen in severe chronic pancreatitis from pancreatic malignancy.
Elastography in differentiating benign and malignant lymph nodes Conventional EUS criteria for detecting malignant lymph nodes (hypoechoic structure, round shape, clear margins and >10 mm in size) carry an accuracy of 50–100%.7 This can be further increased with the use of FNA. However, the use of elastography may play a role in targeting lymph nodes for FNA. In a meta-analysis assessing the effectiveness of elastography in differentiating benign and malignant lymph nodes, a pooled sensitivity and specificity of 0.88 (95% CI 0.83–0.92) and 0.85 (95% CI 0.79–0.89) was obtained.8 The area under ROC curve was 0.9456. Thus, elastography can be used during EUS to target for the most suspicious lymph node and to improve the diagnostic yield.
CONTRAST-ENHANCED EUS
C
ONTRAST-ENHANCED EUS (CE-EUS) uses contrast agents that are gas-containing microbubbles that oscillate and transmit acoustic shadow when hit by the ultrasound wave. This allows detection of intratumoral vessels with enhancement of tumor vascularity.3 The use of contrastenhanced harmonic endoscopic ultrasonography (CEHEUS) further improves imaging of vessels with very slow flow without Doppler-related artifacts.9 Currently used contrast agents are second-generation agents and include
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
A
B
New diagnostic modalities for EUS 57
A
Figure 2 Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) imaging showing a hypo-enhancing pancreatic head adenocarcinoma. (a) Conventional B-mode image. (b) CEH image. Arrow indicates pancreatic adenocarcinoma.
B
Figure 3 Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) imaging of a hyper-enhancing pancreatic neuroendocrine tumor. (a) Conventional B-mode image. (b) CEH image.
A
B
SonoVueTM (Bracco, Courcouronnes, France), SonazoidTM (GE Healthcare, PA, USA) that are composed of gases that are less soluble and less likely to leak out from microbubbles and last longer in the circulation.10
CEH-EUS for pancreatic solid lesions Similar to elastography, the main target for CEH-EUS is to differentiate between pancreatic adenocarcinoma and other pancreatic pathologies such as chronic pancreatitis and neuroendocrine tumors. With CEH-EUS, four types of enhancement patterns have been reported previously: nonenhancement, hypo-enhancement, iso-enhancement and hyper-enhancement.11 The hypo-enhancement pattern is most commonly seen in pancreatic adenocarcinoma (Fig. 2). An overall high sensitivity of 94% (95% CI, 0.91–0.95) and specificity of 89% (95% CI, 0.85–0.92) in diagnosing pancreatic adenocarcinoma was reported in a recent metaanalysis.12 In addition, when compared with multi-detector contrast-enhanced computed tomography, CEH-EUS yielded a significantly higher accuracy in diagnosing pancreatic adenocarcinoma that were 1 mm, identification of irregular intratumoral vessels and the presence of perfusion defect obtained a sensitivity of 93.5% and a specificity of 93.2% for diagnosing malignant gallbladder
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
58
A. Y. B. Teoh and R. S. Y. Tang
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
plasms. Furthermore, the use of quantitative analysis may further improve the objectiveness of the assessment.
CONFLICT OF INTERESTS
A Figure 5 Hypo-enhancing thickened bile duct suggestive of cholangiocarcinoma. (a) Conventional B-mode image. (b) Contrast-enhanced harmonic image. Arrow indicates tumor. PV, portal vein.
polyps.16 In addition, the use of contrast enhancement may help to differentiate bile duct thickening seen in benign conditions such as primary or secondary sclerosing cholangitis from that of bile duct carcinoma. The presence of contrast enhancement in the bile duct wall suggests nonneoplastic changes whereas hypo-enhancement is suggestive of malignancy (Fig. 5).17,18
QUANTITATIVE MEASUREMENTS IN ELASTOGRAPHY AND CE-EUS
T
HE MAJOR DRAWBACK of elastography and CE-EUS is the lack of quantitative measurements in earlier EUS systems. This affects the intra-observer and interobserver reproducibility of results. However, quantitative measurements in both techniques are now possible. Quantitative elastography can be done by hue histogram evaluation or strain ratio calculation.13,19 Initial results suggest that the strain ratio obtained from pancreatic malignant tumors is significantly higher than that of inflammatory masses, and a sensitivity of 100% and specificity of 92.9% were obtained.20 In CEH-EUS, quantitative measurement could also be carried out by measurement of the timeintensity curve (TIC) of contrast uptake.21,22 A sensitivity of 93.75% and specificity of 89.74% were obtained when comparing TIC of chronic pseudotumoral pancreatitis to pancreatic adenocarcinoma. Significant differences in values obtained during TIC analysis were present (P < 0.001).18
CONCLUSION
E
LASTOGRAPHY AND CONTRAST-ENHANCEMENT ARE NEW diagnostic modalities that may complement FNA in the assessment of pancreaticobiliary diseases. The use of these techniques may allow earlier detection and characterization of pancreaticobiliary neo-
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Enriquez JL, Wu TS. An introduction to ultrasound equipment and knobology. Crit. Care Clin. 2014; 30: 25–45. 2 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: 344–8. 3 Dietrich CF, Ignee A, Frey H. Contrast-enhanced endoscopic ultrasound with low mechanical index: A new technique. Z. Gastroenterol. 2005; 43: 1219–23. 4 Hirche TO, Ignee A, Barreiros AP et al. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy 2008; 40: 910–7. 5 Ying L, Lin X, Xie ZL, Hu YP, Tang KF, Shi KQ. Clinical utility of endoscopic ultrasound elastography for identification of malignant pancreatic masses: A meta-analysis. J. Gastroenterol. Hepatol. 2013; 28: 1434–43. 6 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: 578–89. 7 Janssen J. (E)US elastography: Current status and perspectives. Z. Gastroenterol. 2008; 46: 572–9. 8 Xu W, Shi J, Zeng X et al. EUS elastography for the differentiation of benign and malignant lymph nodes: A meta-analysis. Gastrointest. Endosc. 2011; 74: 1001–9. 9 Kudo M. Contrast Harmonic Imaging in the Diagnosis and Treatment of Hepatic Tumors. Tokyo: Springer, 2003. 10 Hirooka Y, Itoh A, Kawashima H et al. Contrast-enhanced endoscopic ultrasonography in digestive diseases. J. Gastroenterol. 2012; 47: 1063–72. 11 Kitano M, Kudo M, Yamao K et al. Characterization of small solid tumors in the pancreas: Contrast: The value of contrastenhanced harmonic endoscopic ultrasonography. Am. J. Gastroenterol. 2012; 107: 303–10. 12 Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: A meta-analysis. Gastrointest. Endosc. 2012; 76: 301–9. 13 Gheonea DI, Streba CT, Ciurea T, Sa˘ftoiu A. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastroenterol. 2013; 13: 2. 14 Ohno E, Hirooka Y, Itoh A et al. Intraductal papillary mucinous neoplasms of the pancreas: Differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules. Ann. Surg. 2009; 249: 628–34.
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
15 Park CH, Chung MJ, Oh TG et al. Differential diagnosis between gallbladder adenomas and cholesterol polyps on contrast-enhanced harmonic endoscopic ultrasonography. Surg. Endosc. 2013; 27: 1414–21. 16 Choi JH, Seo DW, Choi JH et al. Utility of contrast-enhanced harmonic EUS in the diagnosis of malignant gallbladder polyps (with videos). Gastrointest. Endosc. 2013; 78: 484–93. 17 Hyodo T, Hyodo N, Yamanaka T, Imawari M. Contrastenhanced intraductal ultrasonography for thickened bile duct wall. J. Gastroenterol. 2001; 36: 557–9. 18 Hyodo N, Hyodo T. Ultrasonographic evaluation in patients with autoimmune-related pancreatitis. J. Gastroenterol. 2003; 38: 1155–61. 19 Sa˘ftoiu A, Vilmann P, Gorunescu F et al. Neural network analysis of dynamic sequences of EUS elastography used for the
New diagnostic modalities for EUS 59
differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest. Endosc. 2008; 68: 1086–94. 20 Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. Quantitative endoscopic ultrasound elastography: An accurate method for the differentiation of solid pancreatic masses. Gastroenterology 2010; 139: 1172–80. 21 Imazu H, Kanazawa K, Mori N et al. Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma. Scand. J. Gastroenterol. 2012; 47: 853–60. 22 Matsubara H, Itoh A, Kawashima H et al. Dynamic quantitative evaluation of contrast-enhanced endoscopic ultrasonography in the diagnosis of pancreatic diseases. Pancreas 2011; 40: 1073–9.
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Copyright of Digestive Endoscopy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
doi: 10.1111/den.12444
Clinical evaluation of new diagnostic modalities of EUS for pancreatobiliary diseases
Clinical evaluation of new diagnostic modalities of endoscopic ultrasound for pancreaticobiliary diseases Anthony Yuen Bun Teoh1 and Raymond Shing Yan Tang2 1
Department of Surgery, Prince of Wales Hospital and 2Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Endoscopic ultrasonography (EUS) is currently an integral tool for work-up of pancreaticobiliary neoplasms. Tissue acquisition by EUS is possible with fine-needle aspiration (FNA) cytology and histology. However, FNA still carries some limitations and risks of complications. The use of image-enhanced EUS may improve detection and characterization of pancreaticobiliary neoplasms and complement FNA. The present article aims to provide an
INTRODUCTION
E
NDOSCOPIC ULTRASONOGRAPHY (EUS) is currently an important tool for the diagnosis of pancreaticobiliary diseases. The modality has the capability of obtaining fine-needle aspiration (FNA) cytology and histology. However, FNA still carries some limitations and risks of complications. Recently, improvements in EUS hardware and programming have provided new options for imageenhanced EUS that may improve detection and characterization of pancreaticobiliary neoplasms. The present article aims to provide an overview of the current development of contrast-enhanced imaging and elastography in EUS and their potential application in the diagnosis of pancreaticobiliary diseases.
WHY DO WE NEED IMAGE ENHANCEMENT IN EUS?
U
LTRASONOGRAPHY IS ONE of the earliest diagnostic modalities used for medical imaging. The technology detects the reflection of high-frequency mechanical sound energy from the target organ to produce gray-scale
bs_bs_banner
Corresponding: Anthony Yuen Bun Teoh, Department of Surgery, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. Email: [email protected] This manuscript is being submitted as an Invited review article for Digestive Endoscopy. Received 17 December 2014; accepted 19 January 2015.
overview of the current development of contrast-enhanced imaging and elastography in EUS and their potential application in the diagnosis of pancreaticobiliary diseases. Key words: contrast-enhanced endoscopic ultrasonography, elastography, image enhanced endoscopic ultrasonography, tissue harmonic imaging
images over a 2D plane.1 The combination of endoscopy and ultrasonography has revolutionized pancreaticobiliary tract imaging; however, EUS still suffers from limitations common to ultrasound technology including inadequate characterization, operator dependency and limited penetration. Tissue acquisition through FNA may help overcome some of these limitations but FNA is associated with risk of needle-track seeding, false negativity, and the procedure may not be desirable in some situations. Recently, improvements in EUS hardware and programming have provided new options for image enhancement during EUS. Contrast-enhancement and elastography are novel modalities that may improve detection and characterization of suspicious lesions. Contrast-enhancement allows characterization of the microvasculature of lesions whereas elastography depicts the stiffness of lesions.2,3 Furthermore, quantitative measurements are possible and this provides nominal assessments of the lesions and may reduce interobserver disagreement.
EUS-ELASTOGRAPHY
G
IOVANNINI ET AL. FIRST described elastography for EUS in 2006.2 The basis of the technology is that many different pathological processes, including inflammation, fibrosis, and cancer, induce alterations in tissue stiffness. The elastic properties of tissues are measured by applying small amounts of stress causing axial displacement of tissues. Pre- and post-compression images are then compared to produce a measurement of strain and real-time display of an
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
55
56
A. Y. B. Teoh and R. S. Y. Tang
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
Table 1 Classification of elastography findings on pancreatic masses Score
Elastography findings
Pathology
1
Homogeneous hypoechoic area (soft, green) Heterogeneous but soft tissue range (green, yellow and red) Largely blue with minimal heterogeneity Hypoechoic central region with a green center surrounded by blue tissue Heterogeneous lesions largely blue but mixed with softer tissue colors (green, red)
Normal pancreatic tissue Fibrosis
2
3 4
5
Small early pancreatic adenocarcinoma Neuroendocrine tumor or pancreatic metastasis Advanced pancreatic adenocarcinoma with necrosis
elastogram. This allows measurement of the ‘hardness’ of the tissue and differentiation between benign (soft) and malignant (hard) tissues. Elastography images can be obtained by both radial and linear echoendoscopes. The region of interest under examination should contain approximately 50% lesion and 50% normal/surrounding tissue to allow for comparison.4 In addition, the effectiveness of elastography in determining the nature of the lesion depends significantly on the types of differential diagnosis under consideration and it is different for each organ or structure.
Elastography in differentiating pancreatic masses The main differential diagnoses in assessing pancreatic masses include pancreatic adenocarcinoma, fibrosis from chronic pancreatitis or neuroendocrine tumor (PNET). In an aim to classify elastography images of each of these conditions, an elastic scoring system was derived (Table 1; Fig. 1).2 With this classification, elastography images of 24 pancreatic masses were evaluated and a sensitivity of 100% and specificity 67% were obtained. Thereafter, multiple studies have assessed the usefulness of elastography in differentiating between normal pancreas, chronic pancreatitis and pancreatic adenocarcinoma and the results from two meta-analyses are available.5,6 In the first meta-analysis, 10 studies including 893 pancreatic masses were analyzed.5 The pooled sensitivity and specificity were 0.98 (95% confidence interval [CI] 0.93–1.00) and 0.69 (95% CI 0.52–0.82) respectively. Results from qualitative and quantitative EUS elastography were similar. The area under receiver operator characteristic (ROC) curve was 0.94. In the other metaanalysis, 1044 patients from 13 studies were included.6 The pooled sensitivity and specificity were 0.95 (95% CI 0.94–
Figure 1 Elastography assessment of pancreatic adenocarcinoma showing a hard lesion.
0.97) and 0.67 (95% CI 0.61–0.73) and the area under ROC curve was 0.9046. These studies concluded that elastography is a reliable tool for characterization of pancreatic mass and complementary to FNA. However, the main drawback was the moderate specificity. This was attributable to the difficulty in differentiating fibrosis seen in severe chronic pancreatitis from pancreatic malignancy.
Elastography in differentiating benign and malignant lymph nodes Conventional EUS criteria for detecting malignant lymph nodes (hypoechoic structure, round shape, clear margins and >10 mm in size) carry an accuracy of 50–100%.7 This can be further increased with the use of FNA. However, the use of elastography may play a role in targeting lymph nodes for FNA. In a meta-analysis assessing the effectiveness of elastography in differentiating benign and malignant lymph nodes, a pooled sensitivity and specificity of 0.88 (95% CI 0.83–0.92) and 0.85 (95% CI 0.79–0.89) was obtained.8 The area under ROC curve was 0.9456. Thus, elastography can be used during EUS to target for the most suspicious lymph node and to improve the diagnostic yield.
CONTRAST-ENHANCED EUS
C
ONTRAST-ENHANCED EUS (CE-EUS) uses contrast agents that are gas-containing microbubbles that oscillate and transmit acoustic shadow when hit by the ultrasound wave. This allows detection of intratumoral vessels with enhancement of tumor vascularity.3 The use of contrastenhanced harmonic endoscopic ultrasonography (CEHEUS) further improves imaging of vessels with very slow flow without Doppler-related artifacts.9 Currently used contrast agents are second-generation agents and include
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
A
B
New diagnostic modalities for EUS 57
A
Figure 2 Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) imaging showing a hypo-enhancing pancreatic head adenocarcinoma. (a) Conventional B-mode image. (b) CEH image. Arrow indicates pancreatic adenocarcinoma.
B
Figure 3 Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) imaging of a hyper-enhancing pancreatic neuroendocrine tumor. (a) Conventional B-mode image. (b) CEH image.
A
B
SonoVueTM (Bracco, Courcouronnes, France), SonazoidTM (GE Healthcare, PA, USA) that are composed of gases that are less soluble and less likely to leak out from microbubbles and last longer in the circulation.10
CEH-EUS for pancreatic solid lesions Similar to elastography, the main target for CEH-EUS is to differentiate between pancreatic adenocarcinoma and other pancreatic pathologies such as chronic pancreatitis and neuroendocrine tumors. With CEH-EUS, four types of enhancement patterns have been reported previously: nonenhancement, hypo-enhancement, iso-enhancement and hyper-enhancement.11 The hypo-enhancement pattern is most commonly seen in pancreatic adenocarcinoma (Fig. 2). An overall high sensitivity of 94% (95% CI, 0.91–0.95) and specificity of 89% (95% CI, 0.85–0.92) in diagnosing pancreatic adenocarcinoma was reported in a recent metaanalysis.12 In addition, when compared with multi-detector contrast-enhanced computed tomography, CEH-EUS yielded a significantly higher accuracy in diagnosing pancreatic adenocarcinoma that were 1 mm, identification of irregular intratumoral vessels and the presence of perfusion defect obtained a sensitivity of 93.5% and a specificity of 93.2% for diagnosing malignant gallbladder
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
58
A. Y. B. Teoh and R. S. Y. Tang
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
plasms. Furthermore, the use of quantitative analysis may further improve the objectiveness of the assessment.
CONFLICT OF INTERESTS
A Figure 5 Hypo-enhancing thickened bile duct suggestive of cholangiocarcinoma. (a) Conventional B-mode image. (b) Contrast-enhanced harmonic image. Arrow indicates tumor. PV, portal vein.
polyps.16 In addition, the use of contrast enhancement may help to differentiate bile duct thickening seen in benign conditions such as primary or secondary sclerosing cholangitis from that of bile duct carcinoma. The presence of contrast enhancement in the bile duct wall suggests nonneoplastic changes whereas hypo-enhancement is suggestive of malignancy (Fig. 5).17,18
QUANTITATIVE MEASUREMENTS IN ELASTOGRAPHY AND CE-EUS
T
HE MAJOR DRAWBACK of elastography and CE-EUS is the lack of quantitative measurements in earlier EUS systems. This affects the intra-observer and interobserver reproducibility of results. However, quantitative measurements in both techniques are now possible. Quantitative elastography can be done by hue histogram evaluation or strain ratio calculation.13,19 Initial results suggest that the strain ratio obtained from pancreatic malignant tumors is significantly higher than that of inflammatory masses, and a sensitivity of 100% and specificity of 92.9% were obtained.20 In CEH-EUS, quantitative measurement could also be carried out by measurement of the timeintensity curve (TIC) of contrast uptake.21,22 A sensitivity of 93.75% and specificity of 89.74% were obtained when comparing TIC of chronic pseudotumoral pancreatitis to pancreatic adenocarcinoma. Significant differences in values obtained during TIC analysis were present (P < 0.001).18
CONCLUSION
E
LASTOGRAPHY AND CONTRAST-ENHANCEMENT ARE NEW diagnostic modalities that may complement FNA in the assessment of pancreaticobiliary diseases. The use of these techniques may allow earlier detection and characterization of pancreaticobiliary neo-
UTHORS DECLARE NO conflict of interests for this article.
REFERENCES 1 Enriquez JL, Wu TS. An introduction to ultrasound equipment and knobology. Crit. Care Clin. 2014; 30: 25–45. 2 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: 344–8. 3 Dietrich CF, Ignee A, Frey H. Contrast-enhanced endoscopic ultrasound with low mechanical index: A new technique. Z. Gastroenterol. 2005; 43: 1219–23. 4 Hirche TO, Ignee A, Barreiros AP et al. Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions. Endoscopy 2008; 40: 910–7. 5 Ying L, Lin X, Xie ZL, Hu YP, Tang KF, Shi KQ. Clinical utility of endoscopic ultrasound elastography for identification of malignant pancreatic masses: A meta-analysis. J. Gastroenterol. Hepatol. 2013; 28: 1434–43. 6 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: 578–89. 7 Janssen J. (E)US elastography: Current status and perspectives. Z. Gastroenterol. 2008; 46: 572–9. 8 Xu W, Shi J, Zeng X et al. EUS elastography for the differentiation of benign and malignant lymph nodes: A meta-analysis. Gastrointest. Endosc. 2011; 74: 1001–9. 9 Kudo M. Contrast Harmonic Imaging in the Diagnosis and Treatment of Hepatic Tumors. Tokyo: Springer, 2003. 10 Hirooka Y, Itoh A, Kawashima H et al. Contrast-enhanced endoscopic ultrasonography in digestive diseases. J. Gastroenterol. 2012; 47: 1063–72. 11 Kitano M, Kudo M, Yamao K et al. Characterization of small solid tumors in the pancreas: Contrast: The value of contrastenhanced harmonic endoscopic ultrasonography. Am. J. Gastroenterol. 2012; 107: 303–10. 12 Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: A meta-analysis. Gastrointest. Endosc. 2012; 76: 301–9. 13 Gheonea DI, Streba CT, Ciurea T, Sa˘ftoiu A. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastroenterol. 2013; 13: 2. 14 Ohno E, Hirooka Y, Itoh A et al. Intraductal papillary mucinous neoplasms of the pancreas: Differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules. Ann. Surg. 2009; 249: 628–34.
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2015; 27 (Suppl. 1): 55–59
15 Park CH, Chung MJ, Oh TG et al. Differential diagnosis between gallbladder adenomas and cholesterol polyps on contrast-enhanced harmonic endoscopic ultrasonography. Surg. Endosc. 2013; 27: 1414–21. 16 Choi JH, Seo DW, Choi JH et al. Utility of contrast-enhanced harmonic EUS in the diagnosis of malignant gallbladder polyps (with videos). Gastrointest. Endosc. 2013; 78: 484–93. 17 Hyodo T, Hyodo N, Yamanaka T, Imawari M. Contrastenhanced intraductal ultrasonography for thickened bile duct wall. J. Gastroenterol. 2001; 36: 557–9. 18 Hyodo N, Hyodo T. Ultrasonographic evaluation in patients with autoimmune-related pancreatitis. J. Gastroenterol. 2003; 38: 1155–61. 19 Sa˘ftoiu A, Vilmann P, Gorunescu F et al. Neural network analysis of dynamic sequences of EUS elastography used for the
New diagnostic modalities for EUS 59
differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest. Endosc. 2008; 68: 1086–94. 20 Iglesias-Garcia J, Larino-Noia J, Abdulkader I, Forteza J, Dominguez-Munoz JE. Quantitative endoscopic ultrasound elastography: An accurate method for the differentiation of solid pancreatic masses. Gastroenterology 2010; 139: 1172–80. 21 Imazu H, Kanazawa K, Mori N et al. Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma. Scand. J. Gastroenterol. 2012; 47: 853–60. 22 Matsubara H, Itoh A, Kawashima H et al. Dynamic quantitative evaluation of contrast-enhanced endoscopic ultrasonography in the diagnosis of pancreatic diseases. Pancreas 2011; 40: 1073–9.
© 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society
Copyright of Digestive Endoscopy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
