"Mechanisms and Biomarkers of Response and Resistance to Current Targeted Therapies in Gastric Cancer"

The study design is prospective and will include patients with gastric tumors referred to Gastroenterology Department from University of Medicine and Pharmacy of Craiova for EUS local staging enrolled during 18 months.

Data collected for each participant will include: Personal data (name, surname, age, sex); results from previous investigations (blood count, liver and renal function tests, tumoral markers, gastroscopy, computed tomography), EUS variables (including CEH-EUS), histological and immunohistochemical findings, TNM and pTNM status (if possible), molecular analysis findings.

Imaging tests All patients will be evaluated by EUS and CEH-EUS, using radial EUS instruments. Prior to the investigation the stomach has to be empty for at least 8 hours. During the examination biopsies will be taken from normal and tumor tissue for gene expression analysis. For EUS examination, the patient will be placed in left lateral position. The EUS scope will be inserted under direct vision, passed by the tumor and examination should begin during withdrawal at 7.5 MHz. The tumor will be characterized describing its echogenicity, echostructure, size, extent into the wall and surrounding structures, and it will be staged using the modification of the TNM classification. The presence/absence of power Doppler signals will be noted. All lymph nodes will be reported with their maximal size, echogenicity, shape and margins. Nodes larger than 5 mm in diameter, with hypoechoic appearance, round shape (rather than ovoid or flat), sharply demarcated borders and located nearby the tumor will be suspected for malignancy.

CEH-EUS procedure: A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the contrast harmonic image on the left side will be used, according to pre-established presets. The examination will be performed at a low mechanical index (dynamic wide-band contrast harmonic imaging mode) of 0.2. The starting point of the timer will be considered the moment of intravenous contrast injection (SonoVue 2,4 mL), with the whole movie (T0-T120s) recorded on the embedded HDD of the ultrasound system for later analysis. Parameters for objective measurement of tumor perfusion will include maximum intensity of enhancement, mean transit time, time to peak (wash-in time), wash-in slope, area under the curve, representing indirectly blood flow or blood volume in GC patients.

Complications may occur during EUS, but they are rare. These consist of bleeding at the biopsy site which is usually minimal, self-limited and rarely requires follow-up. Perforation of the stomach is extremely rare. The safety profile of the ultrasound contrast agent (Sonovue®) showed a very low incidence of side effects. It is not nephrotoxic and the incidence of hypersensitivity or severe allergic events is lower than with current X-ray agents and comparable to that of other magnetic resonance contrast agents. Sono-Vue is approved for clinical use in EU countries.