Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study

Background and study aims: Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope.

Patients and methods: 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months.

Results: The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS.

Conclusions: CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

References

• 1 Vanbeckevoort D. Solid pancreatic masss: benign or malignant.  JBR-BTR. 2007;  90 487-489
• 2 Carter D C. Cancer of the head of pancreas or chronic pancreatitis? A diagnostic dilemma.  Surgery. 1992;  111 602-603
• 3 Taylor B. Carcinoma of the head of the pancreas versus chronic pancreatitis: diagnostic dilemma with significant consequences.  World J Surg. 2003;  27 1249-1257
• 4 Wharton S M, Rahman Z, Johnson C D. Missed curable carcinoma of the pancreas presenting as chronic pancreatitis.  Postgrad Med J. 1997;  73 577-579
• 5 Hartmann D, Schilling D, Bassler B. et al . ERCP and MRCP in the differentiation of pancreatic tumors.  Dig Dis. 2004;  22 18-25
• 6 Boll D T, Merkle E M. Differentiating a chronic hyperplastic mass from pancreatic cancer: a challenge remaining in multidetector CT of the pancreas.  Eur Radiol. 2003;  13 Suppl 5 M42-M49
• 7 DeBacker A I, Mortele K J, Ros R R. et al . Chronic pancreatitis: diagnostic role of computed tomography and magnetic resonance imaging.  JBR-BTR. 2002;  85 304-310
• 8 Schima W. MRI of the pancreas: tumours and tumour-simulating processes.  Cancer Imag. 2006;  6 199-203
• 9 Brand B, Pfaff T, Binmoeller K F. et al . Endoscopic ultrasound for differential diagnosis of focal pancreatic lesions, confirmed by surgery.  Scand J Gastroenterol. 2000;  35 1221-1228
• 10 Bhutani M S, Hawes R H, Baron P L. et al . Endoscopic ultrasound-guided fine-needle aspiration of malignant pancreatic lesions.  Endoscopy. 1997;  29 854-858
• 11 Chang K, Nguyen P, Erickson R. et al . The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma.  Gastrointest Endosc. 1997;  45 387-394
• 12 Giovannini M. Guided puncture-biopsy under endosonography.  Gastroenterol Clin Biol. 1997;  21 355-357
• 13 Gress F G, Hawes R H, Savides T J. et al . Endoscopic ultrasound-guided fine-needle aspiration biopsy using linear array and radial scanning endosonography.  Gastrointest Endosc. 1997;  45 243-250
• 14 Wiersema M J, Vilmann P, Giovannini M. et al . Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment.  Gastroenterology. 1997;  112 1087-1095
• 15 Williams D B, Sahai A V, Aabakken L. et al . Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience.  Gut. 1999;  44 720-726
• 16 Fritscher-Ravens A, Schirrow L, Atay Z. et al . Endosonographically controlled fine needle aspiration cytology – indications and results in routine diagnosis.  Z Gastroenterol. 1999;  37 343-351
• 17 Voss M, Hammel P, Molas G. et al . Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses.  Gut. 2000;  46 244-249
• 18 Gress F, Gottlieb K, Sherman S. et al . Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer.  Ann Intern Med. 2001;  134 459-464
• 19 Harewood G C, Wiersema M J. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses.  Am J Gastroenterol. 2002;  97 1386-1391
• 20 Eloubeidi M A, Chen V K, Eltoum I A. et al . Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications.  Am J Gastroenterol. 2003;  98 2663-2668
• 21 Raut C P, Grau A M, Staerkel G A. et al . Diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration in patients with presumed pancreatic cancer.  J Gastrointest Surg. 2003;  1 118-126
• 22 Wilson J L, Kalade A, Prasad S. et al . Diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration.  Intern Med J. 2009;  39 32-37
• 23 Dietrich C F. Characterisation of focal liver lesions with contrast enhanced ultrasonography.  Eur J Radiol. 2004;  51S S9-S17
• 24 Bachmann M, Bang N. Contrast enhanced ultrasound in liver imaging.  Eur J Radiol. 2004;  51S S3-S8
• 25 Dietrich C F, Ignee A, Trojan J. et al . Improved characterisation of histologically proven liver tumours by contrast enhanced ultrasonography during the portal venous and specific late phase of SHU 508A.  Gut. 2004;  53 401-405
• 26 Rettenbacher T. Focal liver lesions: role of contrast-enhanced ultrasound.  Eur J Radiol. 2007;  64 173-182
• 27 Morin S, Lim A, Cobbold J. et al . Use of second generation contrast-enhanced ultrasound in the assessment of focal liver lesions.  World J Gastroenterol. 2007;  13 5963-5970
• 28 De Jong N, Frinking P, Bouakaz A. et al . Detection procedures of ultrasound contrast agents.  Ultrasonics. 2000;  38 87-92
• 29 Hirooka Y, Goto H, Ito A. et al . Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: A preliminary study.  Am J Gastroenterol. 1998;  93 632-635
• 30 Dietrich C F, Ignee A, Braden B. et al . Improved differentiation of pancreatic tumors using contrast enhanced endoscopic ultrasound.  Clin Gastroenterol Hepatol. 2008;  6 590-597
• 31 Becker D, Strobel D, Bernatik T. et al . Echo-enhanced and color- and power- Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma.  Gastrointest Endosc. 2001;  53 784-789
• 32 Hocke M, Schulze E, Gottschalk . et al . Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer.  World J Gastroenterol. 2006;  12 246-250
• 33 Hocke M, Ignee A, Topalidis T. et al . Contrast-enhanced endosonographic Doppler spectrum analysis is helpful in discrimination between focal chronic pancreatitis and pancreatic cancer.  Pancreas. 2007;  35 286-288
• 34 Hocke M, Schmidt C, Zimmer B. et al . Contrast enhanced endosonography for improving differential diagnosis between chronic pancreatitis and pancreatic cancer.  Dtsch Med Wochenschr. 2008;  133 1888-1892
• 35 Sakamoto H, Kitano M, Suetomi Y. et al . Utility of contrast-enhanced endoscopic ultrasonography for diagnosis of small pancreatic carcinomas.  Ultrasound Med Biol. 2008;  34 525-532
• 36 Kitano M, Sakamoto H, Matsui U. et al . A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS.  Gastrointest Endosc. 2008;  67 141-149
• 37 Hosoki T. Dynamic CT on pancreatic tumors.  AJR Am J Roentgenol. 1983;  140 959-965
• 38 Freeny P C, Marks W M, Ryan J A. et al . Pancreatic adenocarcinoma: diagnosis and staging with dynamic CT.  Radiology. 1988;  166 125-133
• 39 Johnson P T, Outwater E K. Pancreatic carcinoma versus chronic pancreatitis: dynamic MR imaging.  Radiology. 1999;  212 213-218
• 40 Linder S, Blåsjö M, Rosen A. et al . Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma.  Pancreas. 2001;  22 240-247
• 41 Gritzmann N, Macheiner P, Hollerweger A. et al . CT in the differentiation of pancreatic neoplasms – progress report.  Dig Dis. 2004;  22 6-17
• 42 Claudon M, Cosgrove D, Albrecht T. et al . Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008.  Ultraschall Med. 2008;  29 28-44
• 43 Nagase M, Furuse J, Ishii H. et al . Evaluation of contrast enhancement patterns in pancreatic tumors by coded harmonic sonographic imaging with a microbubble contrast agent.  J Ultrasound Med. 2003;  22 789-795
• 44 Hohl C, Schmidt T, Haage P. et al . Phase-inversion tissue harmonic imaging compared with conventional B-mode ultrasound in the evaluation of pancreatic lesions.  Eur Radiol. 2004;  14 1109-1117
• 45 Kitano M, Kudo M, Maekawa K. et al . Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography.  Gut. 2004;  53 854-859
• 46 D’Onofrio M, Martone E, Malagò R. et al . Contrast-enhanced ultrasonography of the pancreas.  J Pancreas. 2007;  8 Suppl 71-76
• 47 Kitano M, Sakamoto H, Maekawa K. et al . Preliminary study of contrast-enhanced harmonic endosonography with second-generation contrast agents.  J Med Ultrasonics. 2008;  35 11-18
• 48 Strobel D, Hahn E G, Becker D. Harmonic imaging for improving diagnosis of liver tumors – preliminary report.  Z Gastroenterol. 2001;  39 287-289
• 49 Strobel D, Raeker S, Martus P. et al . Phase inversion harmonic imaging versus contrast-enhanced power Doppler sonography for the characterization of focal liver lesions.  Int J Colorect Dis. 2003;  18 63-72
• 50 Giovannini M, Hookey L C, Bories E. et al . Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients.  Endoscopy. 2006;  38 344-348
• 51 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
• 52 Hirche T O, Ignee A, Barreiros A P. et al . Indications and limitations of endoscopic ultrasound elastography for evaluation of local pancreatic lesions.  Endoscopy. 2008;  49 910-917
• 53 Saftoiu 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
• 54 Bournet B, Souque A, Senesse P. et al . Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis.  Endoscopy. 2009;  41 552-557
• 55 Bhutani M S. Digital analysis of EUS images: “promising” method, but is it ready for “prime time”?.  Gastrointest Endosc. 2008;  67 868-70
• 56 Esteban J M, Gil J. Therapeutic effect of chemoembolization therapy on hepatocellular carcinoma: evaluation with contrast-enhanced power Doppler sonography and contrast-enhanced harmonic imaging.  Acad Radiol. 2002;  Suppl 2 S382-S383
• 57 Korpanty G, Carbon J G, Grayburn P. et al . Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature.  Clin Cancer Res. 2007;  13 323-330
• 58 Hernot S, Klibanov A L. Microbubbles in ultrasound-triggered drug and gene delivery.  Adv Drug Deliv Rev. 2008;  60 1153-1166