Abstracts / Pancreatology 14 (2014) S1eS129 S109

Patients & methods: Data from 1 January 2012 to 30 January 2014were retrospectively analyzed.

Results: In 43 patients with borderline resactable pancreatic cancerpancreatoduodenectomy with portal vein reconstruction was performed.In 8 patients end to end anasthomosis, in 6 left renal grafting, in 16reconstruction with using Gore-Tex graft and in 13 plastic surgery of thevessel were performed. Reoperation within one month of the initial oper-ation was performed in 8 patients. The overall mortality rate was 7% (3patients). In 28% (12 patients) margine-negative resection was performed;in 50% patients with end to end anasthomosis.

Conclusion: Borderline resectable pancreatic cancer is challengingdisease for high volume centers. Portal vein resection is standard surgicalprocedure for borderline pancreatic tumors. It is a safe procedure with 18%onset of comorbidity The onset of margine-positive resection is high evenafter vessel resection. Therefore neoadjuvant chemotherapy needs to beconsidered parallel with an optimal surgical approach.

F-076.

Carbon ion beam combined with gemcitabine remarkably disruptspancreatic cancer stem-like cells via complex DNA double strandbreaks (DSBs) and multiple cell death pathways

Sei Sai, Toshiyuki Shirai

Medical Physics Research Program, Research Center for ChargedParticle Therapy, National Institute of Radiological Sciences, Japan

Background: Pancreatic cancers are known to be highly resistance tochemo-radiotherapy and difficult to get good outcome.

Aims: To elucidate whether carbon ion beam combined with gemci-tabine has advantages over X-ray in targeting putative pancreatic cancerstem cells (CSCs).

Materials & methods: CSCs sorted from PANC1 and PK45 cells weretreated with carbon ion beam, X-ray alone or in combination with gemcita-bine, and then colony, spheroid and tumor formation assays, RT Profiler PCRArray assay, and immunofluorescence gH2AX foci assay were performed.

Results: The colony, spheroid formation as well as tumorigenicityassays confirmed that CD44+/ESA+ cells exactly have CSC propertiescompared to CD44-/ESA- cells. The number of colony and spheroid formedfrom CSCs was extremely suppressed by carbon ion beam in combinationwith gemcitabine compared to that of X-ray. The RBE values for the carbonion beam relative to X-ray at the D10 levels for CSCs were 2.13-2.78. Theexpressions of apoptosis-related (Bax, Cytochrome c), autophagy-related(LC3, p62), and senescence-related (p21) genes were remarkably inducedafter carbon ion beam combined with gemcitabine compared to X-raycombined with gemcitabine. Not only the number but also the size ofgH2AX foci in CSCs were lager 24 h after carbon ion beam combined withgemcitabine compared to X-ray combined with gemcitabine.

Conclusion: Carbon ion beam combined with gemcitabine has superiorpotential to kill pancreatic CSCs via unrepairable clustered DSBs, and mul-tiple cell death pathways compared to X-ray combined with gemcitabine.

F-077.

Gemcitabine plus parenteral omega-3 fatty acids can improve qualityof life in patients with advanced pancreatic cancer

John Isherwood a, Ali Arshad a, Francois Runau a, Jill Cooke a, CristinaPollard a, William Steward b, Matthew Metcalfe a, Ashley Dennison a

a University Hospitals of Leicester, Dept of HPB Surgery, UnitedKingdombUniversity Hospitals of Leicester, Dept of Oncology, United Kingdom

Background: Advanced pancreatic cancer is characterised by pro-gressive decline in quality of life (QOL) mediated by pro-inflammatorycytokines. Marine omega-3 fatty acids (n-3FA) are proven to improve QOLin APC patients through attenuation of the pro- inflammatory cascade, butbioavailability and compliance with oral preparations is variable. This is thefirst trial of intravenous n-3FA therapy in cancer patients.

Aims: To assess changes in QOL in APC patients treated with gemcita-bine and intravenous n-3FA.

Materials&methods: Patients with histologically proven unresectableAPC were enrolled in a single-arm trial to receive gemcitabine plus anintravenous n-3FA (up to 100g/week). Validated EORTC QLQ-C30 and PAN-26 questionnaires were used to collect QOL data. Clinical Benefit Response(CBR) rates defined by improvement in global health, pain, weight or QOLscores sustained for at least 5 weeks without decline in any other domainwere recorded.

Results: 50 patients were recruited: 36 were evaluable for QOL changesover at least 5 weeks. Improvement from baseline of at least 10% (clinicallysignificant) and 20% (highly clinically significant) and percentage ofpatients experiencing them were observed in the following domains:Global Health- 47% and 39%, Summated QOL- 39% and 19%, pain scores- 58%and 31% respectively. CBR was observed in 33% with a median duration of18 weeks.

Conclusion: The combination of n-3FA plus gemcitabine can improveQOL in APC patients and the proportion of patients experiencing clinicallysignificant improvement is much higher than previously reported studies.The independent contribution of n-3FA warrants further study in largescale randomised controlled trials.

F-078.

Gemcitabine and tegafur combination in adjuvant treatment of pan-creatic cancer patients with low expression of hENT1

Oleksii Dronov a, Sergii Zemskov a, Yevgenia Kryuchina a, Peter Bakunets a,Maryna Zemskova b

a Bogomolets National Medical University, Ukraineb Kiev City Hospitak #10, Ukraine

Background: hENT1 plays key role in cellular metabolism of gemcita-bine. hENT1 high expression correlates with tumor response on gemcita-bine. hENT1 is predictive but not prognostic marker. Tegafur-dependentinhibition of thymidylatesyntase induces hENT1 and increases gemcitabineuptake by pancreatic cancer (PC) cells. Gemcitabine monotherapy isstandard for adjuvant treatment. About 60% of PC cases represent lowhENT1 expression cells, consequently treatment is effective in 40% ofpatients.

Aims: To investigate efficacy of Tegafur+Gemcitabine (TG) combina-tion in adjuvant treatment of patients after curative resection of pancre-atic adenocarcinoma with low hENT1 expression. Overall survival (OS)and progression free survival (PFS) was analyzed in 2 groups of patients:group treated with gemcitabine monotherapy (GM) and group treatedwith TG.

Patients & methods: GM group consisted of 10 patients with lowhENT1 expression treated from 2010 until 2012. TG group consisted of 10patients treated from 2012 until 2014. hENT1 expression was detectedimmunohistochemically (IHC) using SP120 monoclonal antibody. Results“++” and “+++” were considered as high expression and “+” and “-“ as lowexpression. Ductal adenocarcinoma of pancreas was verified histologicallyin all cases.

Results: Median PFS in GM group and TG group were 9 and 15 monthscorr. (p<0.05, log rank). Median OS in GM group was 17 months andmedian OS in TG group was not reached by the time of analysis.

Abstracts / Pancreatology 14 (2014) S1eS129S110

Conclusion: Clear trend in PFS increase in pancreatic cancer patientswith low grade hENT1 expression treated with TG in adjuvant setting wasrevealed. Large-scale study is needed to prove our results and hypothesis.

F-079.

Results of up-front surgery combined with adjuvant chemotherapy forpancreatic head cancer: Adjuvant gemcitabine chemotherapy may bemore effective for borderline resectable cases.

Taku Aoki a, Takeyuki Watadani b, HIroyuki Akai b, Yoshihiro Sakamoto a,Yasuhiko Sugawara a, Kiyoshi Hasegawa a, Norihiro Kokudo a

aHeapto-Biliary-Pancreatic Surgery Division, Department of Surgery,the University of Tokyo, JapanbDepartment of Radiology, the University of Tokyo, Japan

Background: Surgical resection is the only curative treatment forpancreatic cancer. However, controversies still exist as for the timing ofthe operation, and the indications for neoadjuvant and adjuvanttherapies.

Aims: The aim of the present study was to estimate our strategy of up-front surgery with adjuvant Gemcitabine (GEM) chemotherapy, focusing onthe local extension of the tumors.

Patients & methods: This is a retrospective cohort study. (1) Theoverall and disease-free survival were estimated focusing on the adjuvantGEM chemotherapy (n¼166). (2) The preoperative CT imaging of 93patients with pancreatic head cancer were re-estimated and the outcomeswere compared between resectable (R, n¼47) and borderline resectable(BR, n¼46) groups.

Results: The overall 3-, and 5-year survival rate was 43.1%, and 37.0%,respectively (n¼166). The adjuvant GEM chemotherapy prolonged thedisease-free survival both in the head and body-tail cancer, but the benefitfor overall survivals were not confirmed. In the subgroup analysis, thetumor stage was more advanced in the BR group than the R group. How-ever, the benefit of GEM chemotherapy was more evident in the BR group,and the outcome was better in the BR group. The pattern of recurrence wassimilar between the two groups.

Conclusion: A relatively good disease-free survival was provided byadjuvant GEM chemotherapy. This strategy was more effective in BR cases,but the exact reasons remain to be clarified. Recently, neoadjuvant therapyis frequently indicated for BR cases, but some resectable cases should alsobe indicated for neoadjuvant therapy.

F-080.

Neoadjuvant chemoradiotherapy with S-1 in patients with borderlineresectable pancreatic cancer

Dai Shimizu, Tsutomu Fujii, Masashi Hattori, Masaya Suenaga, SuguruYamada, Mitsuro Kanda, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka,Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara,Yasuhiro KOdera

Department of Gastroenterological Surgery (Surgery II), Japan

Background: The efficacy of neoadjuvant chemoradiotherapy (NACRT)is controversial.

Aims: This study aims to investigate the efficacy and safety of NACRTwith S-1 followed by surgery for the treatment of borderline resectablepancreatic cancer that involved the major visceral artery or the portalvenous system.

Patients & methods: Twenty-eight patients with pancreatic cancersthat abutted the SMA in 10, the CHA in 7, the both SMA and CHA in 1, andoccluded the SMV/PV in 10 were treated with NACRT at a single institution.Radiation therapy was delivered at a total dose of 50.4 Gy in 28 fractions. S-1 was administered orally at a dose of 80 mg/m2/day for 14 consecutivedays followed by a 7-day rest period during radiation therapy. After radi-otherapy and 2 courses of S-1, restaging was done to evaluate secondaryresectability.

Results: Of the all patients, 25 underwent a full course of NACRT, andNACRT terminated in 3 patients because of grade 3 leukopenia in 2 andtumor bleeding in 1. Partial response was achieved in 3 patients and stabledisease in 22. Twenty-four patients (86%) underwent surgical resection,and all had margin-negative (R0) resections. Only two patients (8%) hadmajor morbidity as Clavien-Dindo’s classification III or more, and there wasno operative or in-hospital mortality. Pathological examination revealedthat more than 50% of tumor cells had disappeared in 14 cases and all casesachieved Evans’ score IIa and more.

Conclusion: NACRT with S-1 was feasible and promising therapy forborderline resectable pancreatic cancer that involves the major artery orthe portal venous system.

F-081.

Fasting cycles potentiates the efficacy of gemcitabine treatment in invitro and in vivo pancreatic cancer models

Valerio Pazienza a, Manlio Vinciguerra b, Martina D'Aronzo a, TommasoMazza c, Angelo Andriulli a

a Gastroenterology Unit, IRCCS "Casa SOllievo della Sofferenza" Hospital(Italy), ItalybUniversity College of London, United KingdomcUnit of Bioinformatics Mendel laboratory Rome, Italy

Background: Pancreatic cancer (PC) is ranked as the fourth leadingcause of cancer-related deaths worldwide. Despite many advances inmodern medicine, a modest impact on the outcome of the disease isobserved so far.

Aims: The aim of this study was to assess the effect of fasting cycles ongemcitabine efficacy in vitro and in an in vivo pancreatic cancer xenograftmouse model.

Materials&methods: BxPC3, MiaPaca, Panc1 cells were cultured in adlibitum and in fasting mimicking condition to evaluate the gemcitabineeffect on apoptosis, cell migration. Pancreatic cancer mice xenograft weresubjected to 24h starvation prior to gemcitabine injection to then assessthe tumor volume and weight as compared to ad libitum mice.

Results: fasted pancreatic cancer cells show increased equilibrativenucleoside transporter (hENT1) levels as compared to those cultured in adlibitum medium. Moreover, gemcitabine was more effective on fasted cellsas compared to ad libitum cells in inhibiting cell migration and in inducingcell death as well as, xenograft pancreatic cancer mice displayed a decreaseof 45% in tumor growth when subjected to fasting cycles prior gemcitabineinjection.

Conclusion: Fasting cycles enhance gemcitabine effect in in vitro and inthe in vivo PC mouse xenograft model. These results suggest that fasting orfasting-mimicking interventions could enhance the efficacy of existingcancer treatments in pancreatic cancer patients.

F-082.

Performance of therapy concepts with curative intent in locally ad-vanced pancreatic cancer

Christoph Ansorge a, Gabriel Saliba a, Masoud Karimi b, Nikolaos Kartalis c,Marco Del Chiaro a, Lars Lundell a, John Blomberg a, Ralf Segersv€ard a

a Karolinska University Hospital, Department of GastrointestinalSurgery, SwedenbKarolinska University Hospital, Department of Oncology, SwedencKarolinska University Hospital, Department of Radiology, Sweden

Background: Currently, treatment of locally advanced pancreatic can-cer (LAPC) is characterized by substantial heterogeneity due to variation ofdefinitions, regimes and procedures. Based on mesenteric and hepaticvessel involvement, our radiological resectability assessment distinguishesbetween primarily (B-tumors) and potentially resectable LAPC (after neo-adjuvant chemoradiotherapy, NACRT, C-tumors).

Aims: To evaluate the performance of these two therapy concepts.