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  • br Published by Elsevier Ltd on behalf of Editrice Gastroenterologica


    1590-8658/© 2019 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
    Please cite this article in press as: Tanaka H, et al. Contrast-enhanced harmonic endoscopic ultrasonography for evaluating the response to chemotherapy in pancreatic cancer. Dig Liver Dis (2019),
    G Model
    Table 1
    Patient characteristics.
    TNM classification
    CE-CT; contrast-enhanced computed tomography, CH-EUS; contrast-enhanced harmonic endoscopic ultrasonography, FOLFIRINOX; fluorouracil, leucovorin, irinotecan and oxaliplatin, GEM; gemcitabin, GEM + nab-PTX; gemcitabine + nab-Paclitaxel, GEM + TS1; gemcitabine + Tegafur, Gimeracil, Oteracil, SD; stable diseases, PD; progressive diseases, PR; partial response, TS1; Tegafur, Gimeracil, Oteracil.
    a Mean tumor sizes determined by CH-EUS before (P = 0.347) and after (P = 0.714) chemotherapy were compared with those determined by CE-CT using the t-test.
    b Treatment duration was defined as the Necrostatin-1 from the time of CH-EUS before chemotherapy to evaluation of the therapeutic response.
    on CH-EUS, indicating that the avascular area indicates the presence of necrosis [13]. This suggests that the appearance of an avascular area after chemotherapy in patients with PC in the present study was related to cancer cell necrosis induced by chemotherapy. Thus, the appearance of an avascular area in the tumor on CH-EUS after chemotherapy and its prognostic significance were assessed.
    2. Patients and methods
    The present study was a single-center retrospective study. CH-EUS was performed by expert endoscopists. The present study was performed with the approval of the ethics committee of Kindai University Faculty of Medicine.
    The study enrolled 23 patients (mean age, 62.9 years; male to female ratio, 13:10) with PC who underwent chemotherapy in Kindai University Hospital between April 2010 and March 2016 (Table 1). Eighteen out of 23 patients underwent gemcitabine monotherapy. CH-EUS was performed at the same time as CE-CT (within 2 weeks) before chemotherapy and at the time of evalua-tion of the therapeutic response. No patient showed an avascular area on CH-EUS before chemotherapy
    2.3. Contrast-enhanced computed tomography r> Intravenous CE-CT imaging was performed using two-phase CT (Toshiba X-vigor; Toshiba Medical System, Tokyo, Japan) or
    a 64-channel multidetector CT scanner (Light Speed VCT Vision: GE Healthcare, Milwaukee, Wisconsin, USA) with a 5.0 mm image thickness. In the former modality, 100 mL of Iopamiron (iopami-dol; Nihon Schering, Osaka, Japan), with an iodine concentration of 370 mg/mL, was injected. Dynamic acquisition was performed in the early arterial phase (30 s) and portal phase (60 s). In the lat-ter modality, 510 mg of iodine per kg of iodinated contrast material was administered intravenously at a rate of 3–4 mL/s. Scanning was performed during the pancreatic parenchymal phase (at 40 s) and the liver phase (at 70 s) [14].
    2.4. Contrast-enhanced harmonic endoscopic ultrasonography
    The echoendoscope used for CH-EUS was GF-UCT260 (Olympus Medical Systems Co Ltd, Tokyo, Japan), and the EUS images were analyzed using an Aloka ProSound SSD a-10 system (ALOKA Co Ltd, Tokyo, Japan). An extended pure harmonic detection (ExPHD) mode was used; this synthesized the filtered second harmonic components with signals obtained from the phase shift to provide contrast-enhanced harmonic imaging [9,10,15]. A conventional EUS examination was performed initially. When conventional EUS depicted the pancreatic tumor, the imaging mode was changed to ExPHD mode. The transmitting frequency and mechanical index were 4.7 MHz and 0.3, respectively. Sonazoid (Daiichi-Sankyo, Tokyo, Japan) with a dose of 15 mL/kg body weight was used as an ultrasound contrast agent for CH-EUS. Two experienced endosono-graphers (K.K. and M.K.), who performed more than 1000 CH-EUS procedures each, participated in the study. CH-EUS examinations for PC lasted 60 s from the time of injection of the contrast agent. Video sequences of 60 s were stored. For the retrospective review of stored data, the readers were blinded to the clinical findings. Diagnosis of avascular area and measurement of the maximum size of each avascular area were performed simultaneously in con-sultation with two readers during the special review of videos. Therefore, the Kappa value of the two readers for the diagnosis of avascular areas was not calculated in the study.