Abstracts / Pancreatology

Neuroendocrine Tumors (pNET) and ileal carcinoid tumors have differentembryologic origin (foregut and midgut respectively).

Aims: To report the clinical and pathological features of a patient withsyncronous GH secreting pituitary adenoma, primary pancreatic neuro-endocrine tumor and ileal (midgut) carcinoid.

Patients&methods: A 66 years old manwith acromegaly due to a GH-secreting pituitary adenoma who has been previously treated with surgeryand somatostatine analogues, was referred to our center because of theincidental finding at CT-scan of a 8,7 cm round cystic lesion at the pan-creatic tail. Reviewing the imaging, was detected also a 3 cm round solidhypervascular lesion in the mesenteric context and a hypervascular lesionin the lumen of the small gut suggesting a midgut carcinoid with lymph-node metastasis. The patient was asymptomatic. A 68Ga-DOTA-NOC PET/CT showed focal uptake in all three abdominal lesions confirming theirneuroendocrine nature. High serum 5HT levels were found while urinary5-HIAA was normal.

Results: The patient underwent a distal splenopancreatectomy, ilealresection together with excision of themesenteric lesion. The histology andimmunohistochemical examinations confirmed that the cell pattern of thepancreatic NET (5-HT negative, Ki-67 < 1%) was different from the ilealcarcinoid with lymph node metastases. The patient is well 26 months aftersurgery without recurrence.

Conclusion: Syncronous primary neuroendocrine tumor of pancreas(pNET), midgut carcinoid and pituitary adenoma is a very rare associationand in this case were MEN 1 unrelated.

T-108.

Evaluation of tumor response to targeted therapies in precision-cutslices of human pancreatic neuroendocrine tumors

Margot Bucau, J�erome Cros, Vinciane Rebours, Miguel Albuquerque,Val�erie Paradis, S�ebastien Gaujoux, Alain Sauvanet, Eric Raymond,Philippe Ruszniewski, Pierre Bedossa, Anne Couvelard

AP-HP, HUPNVS Beaujon et Bichat et Universit�e Paris Diderot, France

Background: Patients with PNET might benefit from new therapeuticapproaches acting on the mTOR signaling pathway. Culture of precision-cutslices could allow testing these molecules in human tumors allowingpersonalized treatments.

Aims: To analyze the impact of two therapies targeting the mTORpathway (everolimus (EVE) and BEZ235) on tumor apoptosis and activationof key molecules of the mTOR pathway in a model of precision-cut slicesculture of PNET.

Materials&methods: Prospective study including 12 PNET. Fresh tumorswere cut using a tissue slicer and culturedwith EVE and BEZ2351mm for 1 to2 days (D1 and D2), formalin-fixed and cut for immunohistochemistry withcleaved caspase-3, p-Akt, p-mTOR, p4EBP1 and p-S6 antibodies.

Results: As comparedwithuntreated slices,1/apoptotic caspase3+ tumorscells were higher with EVE (D1 p¼0,0156; D2 p¼0,0078) and BEZ235 (D1p¼0,0039; D2 p¼0,002), 2/pemTOR+ tumors cells were reduced with EVE(D1 p¼0,0095; D2 p¼0,00092); p-Akt+ tumor cells were reduced with EVE(D1 p¼0,0156; D2 p¼0,0156) or BEZ235 (D1 p¼0,001; D2 p¼0,0156); p-S6+tumor cells were reduced with EVE (D1 p¼0,0156; D2 p¼0,0078) or BEZ235(D1 p¼0,0156; D2 p¼0,0156) and p-4EBP1+ tumor cells were reduced at D1for both treatments (p¼0,0313 with EVE, p¼0,0039 with BEZ235).

Conclusion: Our study highlights the interest of the technique of tissueculture to test the effect of molecules inhibiting the mTOR signalingpathway in human PNET. The tumor apoptotic response and the activationof the mTOR targets are quantifiable, allowing to identify predictivemarkers of response.

T-109.

5-FU-based Chemotherapy in pancreatic neuroendocrine neoplasms:Predictive and prognostic markers for treatment und survival

Sebastian Krug a, Michael Boch a, Anja Rinke a, Wilhelm Nimphius b,Daniela Müller a, Alexander K€onig a, Thomas M. Gress a, Patrick Michl a

a University Hospital Marburg, Department of Gastroenterology andEndocrinology, GermanybUniversity Hospital Marburg, Institute of Pathology, Germany

Background: Chemotherapy with 5-FU and Streptozotocin (STZ) rep-resents a standard of care for patients with metastatic pancreatic neuro-endocrine neoplasms (PNENs). However, data to identify predictive andprognostic markers are limited.

Aims: Evaluation of clinicopathological characteristics and possiblepredictive and prognostic markers of patients with PNENs.

Patients & methods: We retrospectively analyzed 41 patients withPNEN who were treated at the University Hospital Marburg between2000 and 2013. Dihydropyrimidin-Dehydrogenase (DPD) and Thymidy-lat-Synthase (TS) expression was correlated with treatment response in19 patients who had available tumor tissue and response data. Themedian overall survival (OS) and progression free survival (PFS) werecalculated using Kaplan-Meier and Cox regression methods,respectively.

Results: The median OS in patients receiving 5-FU/STZ was 50months with a median PFS of 23 months. Objective response rate (ORR)and disease control rate (DCR) were 33% and 77%, respectively. Bio-chemical response (p¼.005) and DPD expression (p¼.018) were pre-dictive markers for 5-FU-based chemotherapy. Multivariate analysisidentified Ki-67 and PS as independent risk factors for OS, and, advancedT-stage, Ki-67 �10% as well as PS �1 as independent risk factors forshorter PFS.

Conclusion: DPD expression and biochemical response representpromising predictive biomarkers for response to 5FU based chemotherapy.Age, Ki-67 and PS were independent prognostic markers of OS and PFS inpatients with PNENs.

T-110.

Streptozotocin-based chemotherapy is still alive in patients with neu-roendocrine neoplasms: Predictive and prognostic markers for treat-ment und survival

Sebastian Krug a, Michael Boch a, Anja Rinke a, Daniela Müller a, AlexanderK€onig a, Hanna Daniel b, Thomas M. Gress a, Patrick Michl a

a University Hospital Marburg, Department of Gastroenterology andEndocrinology, GermanybUniversity Hospital Marburg, Institute of Medical Biometrics andEpidemiology, Germany

Background: Chemotherapy with Streptozotocin (STZ) and 5-FU orDoxorubicin (Doc) represents a standard of care for patients with welldifferentiated metastatic neuroendocrine neoplasms, especially for thepancreas (PNENs). However, data to identify predictive and prognosticmarkers are limited.

Aims: Evaluation of clinicopathological characteristics and possiblepredictive and prognostic markers of patients receiving this combination.

Patients & methods: We retrospectively analyzed 77 patients whowere treated at the University Hospital Marburg between 1995 and 2013.

14 (2014) S1eS129 S81