Trial Information

Contrast-harmonic Endoscopic Ultrasound (CH-EUS) for the Diagnosis of Pancreatic Adenocarcinoma: Results of the First Multicenter Prospective Study With Intra- and Interobserver Concordances Evaluation

100 patients with a solid pancreatic mass of indeterminate origin must be prospectively
included in 3 French centers Exclusion criteria: presence of a cystic component greater than
25 % of the total volume of the lesion, pregnancy, lactation, age <18 years, and usual
contraindications to SonoVue® injection.

All EUS procedure will be performed by 5 experienced endosonographers as follows:

1. Conventional gray-scale B-mode and conventional power Doppler EUS to assess the EUS
characteristics of the pancreatic lesion (localization, size, echogenicity, cystic
component), the aspect of the surrounding parenchyma as well as the presence of
proximal duct dilation, vessels infiltration, and collateral veins; tumor and nodes
(uTN) staging. A systematic video of the 2 modes will be recorded.

2. CH-EUS will be performed to assess the microvascularization of the lesion and of the
surrounding parenchyma: the echoendoscope will be placed in front of the pancreatic
lesion and the contrast-specific mode will be engaged with simultaneous monitoring by
fundamental B mode. A mecanical index (MI) of 0.4 will be chose based on previous
studies [4-6]. An intravenous 4.8 ml SonoVue® bolus injection will be administrated
through an antecubital vein, using a 20 Gauges catheter, followed by 20 ml saline
flush. Examination of pancreatic lesion will be evaluated in real time and a video of
each examination will be record and store. The examination lasted up to 3 minutes after
SonoVue® injection to ensure full examination of the lesion in arterial (hyper
echogenicity of the aorta, superior mesenteric, hepatic or splenic arteries) and venous
phases (hyper echogenicity of the splenic-mesenteric-portal vessels). The pancreatic
lesion enhancement pattern will be compare to the adjacent pancreatic parenchyma. We
differentiated 3 patterns: hypo-, iso- or hyperenhancement. The operator classified the
lesion as pancreatic adenocarcinoma (PA) or non PA. Based on previous pilot studies,
lesion in hypoenhancement consider as PA while lesion in hyper or isoenhancement as
non-PA [4-6]. In case of tumors with mixed pattern the lesion was considered as PA if a
significant area (>10% of the surface) is in hypoenhancement.

3. EUS-FNA: a specimen will be obtain from all lesions using a 22 Gauge needle. Final
diagnosis will be based on pathological findings obtained either surgically or by
EUS-FNA. In the absence of histological evidence, follow-up (F-U) of patients for 12
months will be carried out. The diagnosis of PA ruled out if no sign of malignancy
(disease regression or absence of disease progression) present at the end of F-U.

4. Images reviewing: at the end of the study an anonymous digital video recording of each
procedure including B mode, power Doppler mode and CHE mode will be performed.

Statistical analysis. The McNemar test will be use to compare the CH-EUS performance for the
diagnosis of PA to EUS-FNA and final diagnosis. Sensitivity (Se), specificity (Spe),
predictive positive value (PPV), negative predictive value (NPV) and accuracy with 95%
confidence intervals (95%CI) will be calculate. A p value of 0.05 considered statistically
significant. Intra- and interobserver agreements of CH-EUS for the diagnosis of PA will
assess using kappa statistics and associated 95% CI. Depending on Kappa values, agreement
will considered as minor (0.01-0.20), fair (0.21-0.40), moderate (0.41-0.60), high
(0.61-0.80), or almost perfect (0.81-1.00), beyond chance.