Contrast-enhanced harmonic versus standard endoscopic ultrasound-guided fine-needle aspiration in solid pancreatic lesions: a single-center prospective randomized trial

Abstract

Background Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CH-EUS findings combined with EUS-guided fine-needle aspiration (EUS-FNA) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH-EUS-FNA), potentially improving the diagnostic rate of EUS-FNA, but such superiority has not been proved in prospective studies. We aimed to assess whether CH-EUS-FNA is superior to standard EUS-FNA for specific diagnosis of solid pancreatic masses and what factors affect the diagnostic rate.

Methods This randomized controlled study in one tertiary medical academic center included patients with suspected pancreatic solid masses on transabdominal ultrasound or computed tomography (CT) scan. Two passes with a 22-G standard FNA needle were done using EUS-FNA and CH-EUS-FNA in random order, and the visible core obtained was sent for histological analysis. Final diagnosis was based on EUS-FNA or surgical specimen results and on 12-month follow-up by imaging.

Results 148 patients were evaluated. EUS-FNA and CH-EUS-FNA showed diagnostic sensitivities of 85.5 % and 87.6 %, respectively (not significantly different) and the combined sensitivity of the two passes was 93.8 %. The false-negative rate was not significantly different when hypoenhanced or hyperenhanced lesions were compared with the EUS-FNA results. No differences were seen for the results related to location, size, tumor stage, chronic pancreatitis features, or presence of biliary plastic stent.

Conclusions The diagnostic rates for samples obtained using 22-G needles with standard EUS-FNA and CH-EUS-FNA were not statistically significantly different.

Publication History

Received: 22 December 2020

Accepted: 05 May 2020

Article published online:
10 July 2020

• References

• 1 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
• 2 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68: 7-30
• 3 Kleeff J, Korc M, Apte M. et al. Pancreatic cancer. Nat Rev Dis Primers 2016; 2: 16022
• 4 Hampton T. New target for pancreatic cancer treatment shows potential. JAMA 2019; 322: 391-392
• 5 Yoshinaga S, Suzuki H, Oda I. et al. Role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for diagnosis of solid pancreatic masses. Dig Endosc 2011; 23: 29-33
• 6 Dumonceau JM, Deprez PH, Jenssen C. et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated January 2017. Endoscopy 2017; 49: 695-714
• 7 Yamashita Y, Shimokawa T, Napoléon B. et al. Value of contrast-enhanced harmonic endoscopic ultrasonography with enhancement pattern for diagnosis of pancreatic cancer: a meta-analysis. Dig Endosc 2019; 31: 125-133
• 8 Kitano M, Kudo M, Yamao K. et al. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol 2012; 107: 303-310
• 9 Kamata K, Takenaka M, Omoto S. et al. Impact of avascular areas, as measured by contrast-enhanced harmonic EUS, on the accuracy of fine-needle aspiration for pancreatic adenocarcinoma. Gastrointest Endosc 2018; 87: 158-163
• 10 Sidhu PS, Cantisani V, Dietrich CF. et al. The EFSUMB guidelines and recommendations for the clinical practice of contrast-enhanced ultrasound (CEUS) in non-hepatic applications: update 2017 (long version). Ultraschall Med 2018; 39: e2-e44
• 11 Hou X, Jin Z, Xu C. et al. Contrast-enhanced harmonic endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic lesions: a retrospective study. PLoS One 2015; 10: e0121236
• 12 Sugimoto M, Takagi T, Hikichi T. et al. Standard versus contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for diagnosis of solid pancreatic lesions: a prospective randomized trial. Pancreatology 2015; 15: 538-541
• 13 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
• 14 Iwashita T, Yasuda I, Mukai T. et al. Macroscopic on-site quality evaluation of biopsy specimens to improve the diagnostic accuracy during EUS-guided FNA using a 19-gauge needle for solid lesions: a single-center prospective pilot study (MOSE study). Gastrointest Endosc 2015; 81: 177-185
• 15 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
• 16 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
• 17 Mohammad Alizadeh AH, Shahrokh S, Hadizadeh M. et al. Diagnostic potency of EUS-guided FNA for the evaluation of pancreatic mass lesions. Endosc Ultrasound 2016; 5: 30-34
• 18 Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Inform 2014; 48: 193-204
• 19 Bolboacă SD. Medical diagnostic tests: a review of test anatomy, phases, and statistical treatment of data. Comput Math Methods Med 2019; 2019: 1891569
• 20 Mitchell AJ. Sensitivity × PPV is a recognized test called the clinical utility index (CUI+). Eur J Epidemiol 2011; 26: 251-252
• 21 Khan MA, Grimm IS, Ali B. et al. A meta-analysis of endoscopic ultrasound–fine-needle aspiration compared to endoscopic ultrasound–fine-needle biopsy: diagnostic yield and the value of onsite cytopathological assessment. Endosc Int Open 2017; 5: E363-E375
• 22 Fairley KJ, Diehl DL, Johal AS. “Invisible” pancreatic masses identified by EUS by the “ductal cutoff sign”. Endosc Ultrasound 2019; 8: 125-128
• 23 Fusaroli P, Spada A, Mancino MG. et al. Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses. Clin Gastroenterol Hepatol 2010; 8: 629-634
• 24 Seicean A, Badea R, Stan-Iuga R. et al. Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses. Ultraschall Med 2010; 31: 571-576
• 25 Krishna NB, Mehra M, Reddy AV. et al. EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics. Gastrointest Endosc 2009; 70: 70-79
• 26 Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc 2005; 62: 728-736
• 27 Fritscher-Ravens A, Brand L, Knöfel WT. et al. Comparison of endoscopic ultrasound-guided fine needle aspiration for focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis. Am J Gastroenterol 2002; 97: 2768-2775
• 28 Siddiqui AA, Brown LJ, Hong SK. et al. Relationship of pancreatic mass size and diagnostic yield of endoscopic ultrasound-guided fine needle aspiration. Dig Dis Sci 2011; 56: 3370-3375
• 29 Sugiura R, Kuwatani M, Hirata K. et al. Effect of pancreatic mass size on clinical outcomes of endoscopic ultrasound-guided fine-needle aspiration. Dig Dis Sci 2019; 45: 2704-2712
• 30 Uehara H, Sueyoshi H, Takada R. et al. Optimal number of needle passes in endoscopic ultrasound-guided fine needle aspiration for pancreatic lesions. Pancreatology 2015; 15: 392-396
• 31 Bang JY, Hawes R, Varadarajulu S. A meta-analysis comparing ProCore and standard fine-needle aspiration needles for endoscopic ultrasound-guided tissue acquisition. Endoscopy 2016; 48: 339-349
• 32 Ishiwatari H, Sato J, Fujie S. et al. Gross visual inspection by endosonographers during endoscopic ultrasound-guided fine needle aspiration. Pancreatology 2019; 19: 191-195