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Martin Lovecek,1,* Marketa Janatova,2,* Pavel Skalicky,1 Tomas Zemanek,3 Roman Havlik,1 Jiri Ehrmann,4 Ondrej Strouhal,3 Petra Zemankova,2 Klara Lhotova,2 Marianna Borecka,2 Jana Soukupova,2 Hana Svebisova,3 Pavel Soucek,5 Viktor Hlavac,5 Zdenek Kleibl,2 Cestmir Neoral,1 Bohuslav Melichar,3 Beatrice Mohelnikova-Duchonova3 1Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 2Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; 3Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; 4Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen Czech Republic *These authors contributed equally to this work Background: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background.Patients and methods: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients.Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively.Conclusion: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis. Keywords: pancreatic ductal adenocarcinoma, second primary neoplasms, subsequent malignant neoplasm, hereditary cancer genes, long-term survivors, surgical treatment

Purpose: Limited data are available regarding the efficacy of hepatic arterial infusion (HAI) of oxaliplatin in patients with liver metastases from colorectal carcinoma (CRC). The aim of the present study was to evaluate the results of HAI of oxaliplatin combined with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with such metastases., Methods: A retrospective analysis of 22 CRC patients treated with HAI of combination of oxaliplatin and 5-FU and LV was performed., Results: Partial response (PR) was observed in 4 (18%) patients and stable disease (SD) in 7, with an overall disease control rate of 50%. The median progression-free (PFS) and overall survival (OS) were 7 and 11 months, respectively. Two patients treated with first-line treatment underwent subsequent liver resection. In 2 patients, HAI of oxaliplatin, 5-FU and LV was combined with systemic administration of bevacizumab., Conclusion: Our data demonstrate reasonable efficacy of HAI with oxaliplatin, 5-FU and LV in patients with liver metastases from CRC.