BackgroundRecent randomized controlled trials comparing neoadjuvant chemoradiation plus surgery or perioperative chemotherapy plus surgery with surgery alone showed significant survival benefits for combined modality treatment of patients with localized esophageal adenocarcinoma. However, head-to-head comparisons of neoadjuvant chemoradiation and perioperative chemotherapy applying contemporary treatment protocols are lacking. The present trial was initiated to obtain valid information whether neoadjuvant chemoradiation or perioperative chemotherapy yields better survival in the treatment of localized esophageal adenocarcinoma.Methods/designThe ESOPEC trial is an investigator-initiated multicenter prospective randomized controlled two-arm trial, comparing the efficacy of neoadjuvant chemoradiation (CROSS protocol: 41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative chemotherapy and surgery (FLOT protocol: 5-FU/leucovorin/oxaliplatin/docetaxel) for the curative treatment of localized esophageal adenocarcinoma. Patients with cT1cN + cM0 and cT2-4acNxcM0 esophageal and junctional adenocarcinoma are eligible. The trial aims to include 438 participants who are centrally randomized to one of the two treatment groups in a 1:1 ratio stratified by N-stage and study site. The primary endpoint of the trial is overall survival assessed with a minimum follow-up of 36 months. Secondary objectives are progression-free survival, recurrence-free survival, site of failure, postoperative morbidity and mortality, duration of hospitalization as well as quality of life.DiscussionThe ESOPEC trial compares perioperative chemotherapy according to the FLOT protocol to neoadjuvant chemoradiation according to the CROSS protocol in multimodal treatment of non-metastasized recectable adenocarcinoma of the esophagus and the gastroesophageal junction. The goal of the trial is identify the superior protocol with regard to patient survival, treatment morbidity and quality of life. Trial registrationNCT02509286 (July 22, 2015)Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2564-y) contains supplementary material, which is available to authorized users.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p < 0.001). Patients with >3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS G12V mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.

AIMTo evaluate rebleeding, primary failure (PF) and mortality of patients in whom over-the-scope clips (OTSCs) were used as first-line and second-line endoscopic treatment (FLET, SLET) of upper and lower gastrointestinal bleeding (UGIB, LGIB).METHODSA retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016 (n = 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as < or ≥ 7 and were compared with the original Rockall data. Differences between FLET and SLET were calculated. Univariate and multivariate analysis were performed to evaluate the factors that influenced rebleeding after OTSC placement.RESULTSPrimary hemostasis and clinical success of bleeding lesions (without rebleeding) was achieved in 88/100 (88%) and 78/100 (78%), respectively. PF was significantly lower when OTSCs were applied as FLET compared to SLET (4.9% vs 23%, P = 0.008). In multivariate analysis, patients who had OTSC placement as SLET had a significantly higher rebleeding risk compared to those who had FLET (OR 5.3; P = 0.008). Patients with Rockall risk scores ≥ 7 had a significantly higher in-hospital mortality compared to those with scores < 7 (35% vs 10%, P = 0.034). No significant differences were observed in patients with scores < or ≥ 7 in rebleeding and rebleeding-associated mortality.CONCLUSIONOur data show for the first time that FLET with OTSC might be the best predictor to successfully prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.

Our retrospective analysis shows that reduction of postoperative pulmonary morbidity, perioperative blood loss, and shortening of hospital stay can be achieved by HMIE. The procedure is safe, and the rate of surgical complications and oncological radicality is comparable to the conventional procedure.