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Pancreatic Neoplasms: HELP
Articles by Martin Loveček
Based on 26 articles published since 2010
(Why 26 articles?)
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Between 2010 and 2020, M. Loveček wrote the following 26 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Biomarkers and pathways of chemoresistance and chemosensitivity for personalized treatment of pancreatic adenocarcinoma. 2019

Zemanek, Tomas / Melichar, Bohuslav / Lovecek, Martin / Soucek, Pavel / Mohelnikova-Duchonova, Beatrice. ·Department of Oncology, Faculty of Medicine & Dentistry, Palacky University Olomouc, University Hospital Olomouc, Czech Republic. · Institute of Molecular & Translational Medicine, Faculty of Medicine & Dentistry, Palacky University, Olomouc, Czech Republic. · Department of Surgery I, Faculty of Medicine & Dentistry, Palacky University, Olomouc, University Hospital Olomouc, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. ·Pharmacogenomics · Pubmed #30539680.

ABSTRACT: Pancreatic carcinoma is usually diagnosed late when treatment options are limited and is considered a chemo-resistant malignancy. However, early stage, good performance status and specific patient subgroup are thought to have a more favorable prognosis. Search for novel molecular biomarkers, which could predict treatment resistance, represents a major opportunity, but also a challenge in further research. This review summarizes most aspects of individualized therapy of pancreatic cancer including promising biomarkers, BRCA-deficient pancreatic cancer and its etiology. It may be estimated that nearly a third of metastatic pancreatic ductal adenocarcinoma patients could benefit from treatment other than gold standard chemotherapy. Thus, other aspects of an individualized approach concerning the main factors for the choice of the best therapy for individual pancreatic cancer patient (surgery and chemotherapy), as well as the future directions (target therapy and immunotherapy), are also addressed.

2 Review Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature. 2017

Lovecek, Martin / Skalicky, Pavel / Chudacek, Josef / Szkorupa, Marek / Svebisova, Hana / Lemstrova, Radmila / Ehrmann, Jiri / Melichar, Bohuslav / Yogeswara, Tharani / Klos, Dusan / Vrba, Radek / Havlik, Roman / Mohelnikova-Duchonova, Beatrice. ·Department of Surgery I, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77520 Olomouc, Czech Republic. · Department of Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77520 Olomouc, Czech Republic. · Department of Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, 77520 Olomouc, Czech Republic. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, 77520 Olomouc, Czech Republic. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University, 775220 Olomouc, Czech Republic. ·World J Gastroenterol · Pubmed #29085191.

ABSTRACT: AIM: To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. METHODS: One-hundred-fifty-nine consecutive pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical pancreatic surgery between 2006 and 2013 were included in this retrospective analysis. The clinical data including age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered, and follow-up were all obtained from medical records. Further analysis covered only patients with metachronous metastases. Clinical and histopathological data (age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered and follow-up) of patients with metachronous non-pulmonary metastases and patients with metachronous pulmonary metastases were statistically assessed. Disease-free survival (DFS) from pancreas resection until metastases onset and overall survival (OS) were calculated. Wilcoxon test, χ RESULTS: Metachronous pulmonary metastases were observed in 20 (16.9%) and were operable in 3 (2.5%) of PDAC patients after a prior curative-intent surgery. Patients with isolated pulmonary metastases (oligometastases and multiple metastases) had estimated prior DFS and OS of 35.4 and 81.4 mo, respectively, and those with metachronous pulmonary metastases accompanied by other metastases had prior DFS and OS of 17.3 and 23.4 mo, respectively. Patients with non-pulmonary metastases had prior DFS and OS of 9.4 and 15.8 mo, respectively. Different clinical scenarios according to the presentation of MPM were observed and patients could be divided to three subgroups with different prognosis which could be used for the selection of treatment strategy: isolated pulmonary oligometastases, isolated multiple pulmonary metastases and pulmonary metastases accompanied by other metastases. CONCLUSION: Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.

3 Article Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. 2019

Gentiluomo, Manuel / Puchalt García, Paula / Galeotti, Alice Alessandra / Talar-Wojnarowska, Renata / Tjaden, Christine / Tavano, Francesca / Strobel, Oliver / Kupcinskas, Juozas / Neoptolemos, John / Hegyi, Péter / Costello, Eithne / Pezzilli, Raffaele / Sperti, Cosimo / Lawlor, Rita T / Capurso, Gabriele / Szentesi, Andrea / Soucek, Pavel / Vodicka, Pavel / Lovecek, Martin / Hackert, Thilo / Cavestro, Giulia Martina / Milanetto, Anna Caterina / Canzian, Federico / Campa, Daniele. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Universitat Politècnica de Valéncia, Valencia, Spain. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy. · Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Translational Gastroenterology Research Group, Hungarian Academy of Sciences and University of Szeged (MTA-SZTE), Szeged, Hungary. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · Department of Translational Medicine, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary. · National Institute for Health Research Liverpool, Pancreas Biomedical Research Unit, University of Liverpool, United Kingdom. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital Bologna, Italy. · Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy. · ARC-Net Research Centre, University Hospital G.B. Rossi, University of Verona, Verona, Italy. · Pancreatico/Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, Rome, Italy. · First Department of Medicine, University of Szeged, Szeged, Hungary. · János Szentágothai Research Centre and Centre for Neuroscience, University of Pécs, Pécs, Hungary. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Institute of Experimental Medicine, Czech Academy of Sciences and Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Czech Republic. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University San Raffaele Scientific Institute, Milan, Italy. ·Carcinogenesis · Pubmed #30629142.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, single nucleotide polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types. The aim of this study was to investigate the possible association between SNPs in the ABCC2 gene and overall survival (OS) in PDAC patients. We analysed 12 polymorphisms, including tagging-SNPs covering all the genetic variability of the ABCC2 gene and genotyped them in 1415 PDAC patients collected within the Pancreatic Disease ReseArch (PANDoRA) consortium. We tested the association between ABCC2 SNPs and PDAC OS using Cox proportional hazard models. We analysed PDAC patients dividing them by stage and observed that the minor alleles of three SNPs showed an association with worse OS [rs3740067: hazard ratio (HR) = 3.29, 95% confidence interval (CI) = 1.56-6.97, P = 0.002; rs3740073: HR = 3.11, 95% CI = 1.52-6.38, P = 0.002 and rs717620: HR = 2.90, 95% CI = 1.41-5.95, P = 0.004, respectively] in stage I patients. In patients with more advanced PDAC, we did not observe any statistically significant association. Our results suggest that rs3740067, rs3740073 and rs717620 could be promising prognostic markers in stage I PDAC patients.

4 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University, Rome, Italy. · PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10

5 Article Results of a randomized controlled trial comparing closed-suction drains versus passive gravity drains after pancreatic resection. 2018

Čečka, Filip / Jon, Bohumil / Skalický, Pavel / Čermáková, Eva / Neoral, Čestmír / Loveček, Martin. ·Department of Surgery, Medical Faculty and University Hospital Hradec Králové, Czech Republic. Electronic address: filip.cecka@seznam.cz. · Department of Surgery, Medical Faculty and University Hospital Hradec Králové, Czech Republic. · First Department of Surgery, Medical Faculty and University Hospital Olomouc, Czech Republic. · Department of Medical Biophysics, Medical Faculty Hradec Králové, Charles University, Hradec Králové, Czech Republic. ·Surgery · Pubmed #30082139.

ABSTRACT: BACKGROUND: This dual-center, randomized controlled trial aimed to compare 2 types of intra-abdominal drains after pancreatic resection and their effect on the development of pancreatic fistulae and postoperative complications. METHODS: Patients undergoing pancreatic resection were randomized to receive either a closed-suction drain or a closed, passive gravity drain. The primary endpoint was the rate of postoperative pancreatic fistula. A secondary endpoint was postoperative morbidity during follow-up of 3 months. The planned sample size was 223 patients. RESULTS: A total of 294 patients were assessed for eligibility, 223 of whom were randomly allocated. One patient was lost during follow-up, and 111 patients in each group were analyzed. The rate of postoperative pancreatic fistula (closed-suction 43.2%, passive 36.9%, P = .47) and overall morbidity (closed-suction 51.4%, passive 40.5%, P = .43) were not different between the groups. We did not find any differences between the groups in reoperation rate (P = .45), readmission rate (P = .27), hospital stay (P = .68), or postoperative hemorrhage (P = .11). We found a significantly lesser amount of drain fluid in the passive gravity drains between the second and fifth postoperative days and also on the day of drain removal compared with closed-suction drains. CONCLUSION: The type of drain (passive versus closed suction) had no influence on the rate of postoperative pancreatic fistulae. The closed-suction drains did not increase the rate of postoperative complications. We found that the passive gravity drains are more at risk for obstruction, whereas the closed-suction drains kept their patency for greater duration.

6 Article Tumor grade as significant prognostic factor in pancreatic cancer: validation of a novel TNMG staging system. 2018

Hlavsa, J / Cecka, F / Zaruba, P / Zajak, J / Gurlich, R / Strnad, R / Pavlik, T / Kala, Z / Lovecek, M. ·Department of Surgery, University Hospital Brno Bohunice and Faculty of Medicine, Masaryk University, Brno, Czech Republic, Czech Republic · Department of Surgery, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Charles University, Hradec Kralove, Czech Republic · Department of Surgery, 2nd Faculty of Medicine of the Charles University and the Military University Hospital Prague, Charles University, Prague, Czech Republic · 3rd Department of Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital, Charles University, Prague, Czech Republic · Department of Surgery, University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic · Institute of Biostatistics and Analysis, Faculty of Medicine and Faculty of Science, Masaryk University, Brno, Czech Republic · Surgery I, University Hospital Olomouc, Palacky University, Olomouc, Czech Republic ·Neoplasma · Pubmed #30064236.

ABSTRACT: Aim of the study was to asses the tumor grade prognostic value in the Czech pancreatic cancer patients and to evaluate the accuracy of TNMG prognostic model. Retrospective analysis of 431 pancreatic cancer patients undergoing pancreatic resection in seven Czech oncological centers between 2003 and 2013 was performed. The impact of tumor grade and the accuracy of TNMG prognostic model were evaluated. Lymph node status, tumor size, tumor stage and grade were proved as statistically significant survival predictors. The lower tumor differentiation (grade 3 and 4) was associated with poorer prognosis in all stages (stage I: HR 2.23 [1.14; 4.36, CI 95%] p=0.019, stage II: HR 3.09 [2.01; 4.77, CI 95%] p=0.001, stage III and IV: HR 3.52 [1.73; 7.18, CI 95%] p=0.001). Kaplan-Meier analysis verified statistically significant impact of new TNMG stages on survival after resection for pancreatic cancer (p=0.001). In conclusion, we can state that the tumor grade was confirmed as statistically significant prognostic factor in pancreatic cancer. Its incorporation into the current TNM classification enables more accurate prognosis prediction within particular clinical stages. That is why an inclusion of the grade to the standard TNM classification should be discussed.

7 Article [The effect of circulating tumor cells on the survival of patients with pancreatic cancer 5-year results]. 2018

Bébarová, L / Skalický, P / Srovnal, J / Prokopová, A / Zapletalová, J / Hajdúch, M / Loveček, M. · ·Rozhl Chir · Pubmed #29444581.

ABSTRACT: INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its incidence increases worldwide and, despite the developments in cancer research, mortality rates have not decreased. Poor prognosis of the disease is due to many factors, mainly late diagnosis. Distant metastases and peritoneal carcinomatosis are caused by hematogenous and lymphogenous spreading of the tumorous cells. One of the factors that may influence patient survival are so-called circulating tumor cells (CTCs). The aim of our work was to evaluate the possible influence of CTCs on the survival of patients with PDAC. METHOD: We included patients who underwent a radical or palliative surgical intervention at the First Department of Surgery of Medical Faculty and University Hospital in Olomouc between 1 January 2008 and 31 December 2012. The required samples for CTCs detection were taken from each patient. The detection of the CTCs was performed using real-time RT-PCR. The results were statistically processed and evaluated. RESULTS: We included 126 patients in total, of which 88 were treated radically and 38 received palliative treatment. Mean age was 63 years in patients with radical and 64 years in patients with palliative surgery. Mean survival time in radically treated patients was 29.6 months, in patients with palliative treatment the mean survival time was 8.5 months. The survival time of radically treated patients with CTCs was 27.2 months, without CTCs it was 33.8 months. CONCLUSION: We did not prove a statistically significant difference in survival between radically treated PDAC patients with and without detected CTCs in our work.Key words: pancreatic cancer - circulating tumor cells survival.

8 Article [Solid pseudopapillary neoplasms of the pancreas]. 2017

Tesaříková, J / Loveček, M / Neoral, Č / Vomáčková, K / Bébarová, L / Skalický, P. · ·Rozhl Chir · Pubmed #28537412.

ABSTRACT: INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a very rare neoplasm that occurs in girls and young women in 90% of cases; the range is 779 years of age, and the median is 28 years of age. This tumour was first described by Virginia Frantz in 1959 as a papillary cystic tumour of the pancreas. METHODS: The aim of this retrospective study was to analyse the incidence of SPN in all patients with a pancreatic tumour operated at the 1st Dept. of Surgery, University Hospital Olomouc between years 2006 and 2015. Clinical symptoms, imaging methods used, tumour marker positivity, histological findings, postoperative complications and disease-free interval were all evaluated. RESULTS: Of the 454 patients operated on between 20062015, the diagnosis of SPN was made in five female patients. The following imaging methods were used in the preoperative diagnostic process: CT, MRI, PET/CT and endosonography. In four patients the tumour was localised in the tail of the pancreas; these women underwent left-sided pancreatectomy. In one patient, the tumour was located in the pancreatic head and a pylorus-preserving pancreaticoduodenectomy was performed. Complications were seen only in one patient who underwent revision on the first postoperative day for bleeding from the pancreatic cut surface. Pancreatic fistula was not observed in any of the patients. The procedures were considered as sufficient from the oncological viewpoint due to the radical resection procedure and negative resection margin, and therefore no adjuvant oncological treatment was indicated in any of the patients. During the follow-up period, recurrence was not observed in any one of the patients. CONCLUSION: Solid pseudopapillary neoplasm of the pancreas is a rare disorder with a low malignant potential occurring primarily in young women. Generally, SPN has a good prognosis; however, advanced stages of the disease with distant metastases may be encountered in rare cases. The only curative treatment is radical surgical resection.Key words: solid pseudopapillary neoplasm Frantzs tumour pancreas.

9 Article [Tumor cells transfer between the patient and laboratory animal as a basic methodological approach to the study of cancerogenesis and identification of biomarkers]. 2016

Klos, D / Stašek, M / Loveček, M / Skalický, P / Vrba, R / Aujeský, R / Havlík, R / Neoral, Č / Varanashi, L / Hajdúch, M / Vrbková, J / Džubák, P. · ·Rozhl Chir · Pubmed #28182438.

ABSTRACT: INTRODUCTION: The investigation of prognostic and predictive factors for early diagnosis of tumors, their surveillance and monitoring of the impact of therapeutic modalities using hybrid laboratory models in vitro/in vivo is an experimental approach with a significant potential. It is preconditioned by the preparation of in vivo tumor models, which may face a number of potential technical difficulties. The assessment of technical success of grafting and xenotransplantation based on the type of the tumor or cell line is important for the preparation of these models and their further use for proteomic and genomic analyses. METHODS: Surgically harvested gastrointestinal tract tumor tissue was processed or stable cancer cell lines were cultivated; the viability was assessed, and subsequently the cells were inoculated subcutaneously to SCID mice with an individual duration of tumor growth, followed by its extraction. RESULTS: We analysed 140 specimens of tumor tissue including 17 specimens of esophageal cancer (viability 13/successful inoculations 0), 13 tumors of the cardia (11/0), 39 gastric tumors (24/4), 47 pancreatic tumors (34/1) and 24 specimens of colorectal cancer (22/9). 3 specimens were excluded due to histological absence of the tumor (complete remission after neoadjuvant therapy in 2 cases of esophageal carcinoma, 1 case of chronic pancreatitis). We observed successful inoculation in 17 of 28 tumor cell lines. CONCLUSION: The probability of successful grafting to the mice model in tumors of the esophagus, stomach and pancreas is significantly lower in comparison with colorectal carcinoma and cell lines generated tumors. The success rate is enhanced upon preservation of viability of the harvested tumor tissue, which depends on the sequence of clinical and laboratory algorithms with a high level of cooperation.Key words: proteomic analysis - xenotransplantation - prognostic and predictive factors - gastrointestinal tract tumors.

10 Article Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. 2016

Campa, Daniele / Pastore, Manuela / Gentiluomo, Manuel / Talar-Wojnarowska, Renata / Kupcinskas, Juozas / Malecka-Panas, Ewa / Neoptolemos, John P / Niesen, Willem / Vodicka, Pavel / Delle Fave, Gianfranco / Bueno-de-Mesquita, H Bas / Gazouli, Maria / Pacetti, Paola / Di Leo, Milena / Ito, Hidemi / Klüter, Harald / Soucek, Pavel / Corbo, Vincenzo / Yamao, Kenji / Hosono, Satoyo / Kaaks, Rudolf / Vashist, Yogesh / Gioffreda, Domenica / Strobel, Oliver / Shimizu, Yasuhiro / Dijk, Frederike / Andriulli, Angelo / Ivanauskas, Audrius / Bugert, Peter / Tavano, Francesca / Vodickova, Ludmila / Zambon, Carlo Federico / Lovecek, Martin / Landi, Stefano / Key, Timothy J / Boggi, Ugo / Pezzilli, Raffaele / Jamroziak, Krzysztof / Mohelnikova-Duchonova, Beatrice / Mambrini, Andrea / Bambi, Franco / Busch, Olivier / Pazienza, Valerio / Valente, Roberto / Theodoropoulos, George E / Hackert, Thilo / Capurso, Gabriele / Cavestro, Giulia Martina / Pasquali, Claudio / Basso, Daniela / Sperti, Cosimo / Matsuo, Keitaro / Büchler, Markus / Khaw, Kay-Tee / Izbicki, Jakob / Costello, Eithne / Katzke, Verena / Michalski, Christoph / Stepien, Anna / Rizzato, Cosmeri / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Division Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. · Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg - Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · ARC-Net Research Centre, and Department of Diagnostics and Public Health University and Hospital Trust of Verona, Verona, Italy. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Epidemiology Unit Nuffield Department of Population Health University of Oxford, Oxford, UK. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Dant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. · Clinical Gerontology Unit, Addenbrooke’s Hospital, School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Laboratory of Clinical, Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. ·Oncotarget · Pubmed #27486979.

ABSTRACT: The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

11 Article [The survival of patients with radically non-resectable pancreatic cancer]. 2016

Bébarová, L / Skalický, P / Klos, D / Havlík, R / Neoral, Č / Zapletalová, J / Loveček, M. · ·Rozhl Chir · Pubmed #27410755.

ABSTRACT: INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its poor prognosis is due to a combination of various factors, mainly aggressive biology of the tumour, non-specific symptoms in early stages, their underestimation, prolonged time to diagnosis and late onset of treatment. The majority of patients are diagnosed in an advanced stage of the disease. Median survival of these patients ranges from 211 months. The most common consequences of locally advanced disease that require intervention include obstruction of the duodenum and biliary obstruction. The purpose of our study was to analyze the survival of patients with radically inoperable PDAC undergoing palliative surgery or exploration with biopsy, and to evaluate the influence of patient and tumour factors and treatment modalities on survival. METHODS: In our retrospective study we included all patients with radically inoperable PDAC undergoing a non-radical surgical intervention between 01 January 2006 and 31 December 2014. Patient age, histopathological findings, surgical and oncological treatment and survival were included in the analysis. The results were statistically processed and evaluated using IBM SPSS Statistics software version 22 (USA). RESULTS: 184 patients with radically inoperable PDAC, 105 males and 79 females, were included in our study. Mean age of the patients was 64 years and most patients presented with stage IV of the disease. Mean survival time was 7.04 months and median 4.7 months. CONCLUSION: We determined a statistically significant influence of the following factors on patient survival: sex, stage, presence of distant metastases at the time of surgery and oncological treatment administration. Mean and median survival of patients with radically inoperable tumours matches global statistics. KEY WORDS: pancreatic cancer - radically non-resectable - palliative surgery - survival.

12 Article [Current status regarding surgical treatment of pancreatic cancer in the Czech Republic]. 2016

Loveček, M / Skalický, P / Ryska, M / Gürlich, R / Hlavsa, J / Čečka, F / Krška, Z / Strnad, R / Peteja, M / Klein, J / Šiller, J / Zajak, J / Krejčí, T / Rupert, K / Kočík, M / Šefr, R / Straka, M / Dušek, L / Jarkovský, J / Havlík, R / Neoral, Č. · ·Rozhl Chir · Pubmed #27226268.

ABSTRACT: INTRODUCTION: The aim is to map the current situation in the surgical treatment of pancreatic cancer in the Czech Republic. This information has been obtained from surgical treatment providers using a simple questionnaire and by identifying the so called high volume centres. The information has been collected in the interest of organizing and planning research projects in the field of pancreatic cancer treatment. METHOD: We addressed centres known to provide surgical treatment of pancreatic cancer. A simple questionnaire formulated one question about the total number of pancreatic resections, also separately for the diagnoses PDAC - C25, in the last two years (2014 and 2015). Other questions focused on the use of diagnostic methods, neoadjuvant therapy, preoperative assessment of risks, the possibility of rapid intraoperative histopathology examination, Leeds protocol, monitoring of morbidity and mortality including long-term results, and the method of postoperative follow-up and treatment. ÚZIS (Institute of Health Information and Statistics of the Czech Republic) was addressed with a request to analyze the frequency of reported total numbers for DPE, LPE, TPE and to do the same with respect to diagnosis C 25 for the last two years, available for the entire Czech Republic (2013, 2014). RESULTS: Altogether 19 institutions were identified by the preceding audit, which reported more than 10 pancreatic resections annually; these institutions were addressed with the questionnaire. Sixteen institutions responded to the questions, 13 of them completely. CONCLUSION: The majority of potentially radical surgeries for PDAC in the Czech Republic are carried out at 6 institutions. All of the institutions that participated in the survey collect data about morbidity and mortality and monitor their results. KEY WORDS: pancreas cancer outcomes surgery.

13 Article Long-term survival after resections for pancreatic ductal adenocarcinoma. Single centre study. 2016

Lovecek, Martin / Skalicky, Pavel / Klos, Dusan / Bebarova, Linda / Neoral, Cestmir / Ehrmann, Jiri / Zapletalova, Jana / Svebisova, Hana / Vrba, Radek / Stasek, Martin / Yogeswara, Tharani / Havlik, Roman. ·Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. · Department of Surgery I, University Hospital Olomouc, Czech Republic. · Department of Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. · Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic. ·Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub · Pubmed #27029600.

ABSTRACT: AIM: To analyse the 5-year survival rate of patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC) and to identify prognostic factors. METHODS: A prospectively maintained database of 90 consecutive patients who underwent radical resection for PDAC was analysed. Survival was evaluated using the Kaplan-Meier method. Log-rank test and Cox regression analysis were used for the evaluation of prognostic factors. P values less than 0.05 were considered significant. RESULTS: Mean age (± standard deviation) was 63.2±8.6 years (female 28.9% and male 71.1%). Tumour localisation was in the head in 76 (84.5%), multifocal in 3 (3.3%) and in the body/tail in 11 (12.2%). Pancreatic head resection was performed in 75 (83.3%), total pancreatectomy in 4 (4.4%) and distal pancreatectomy with splenectomy in 11 (12.2%), with standard lymphadenectomy. Venous resection was in 4 (4.4%). Thirty-day and in-hospital mortality occurred in 1 (1.1%), 90-day mortality was 3.3%. On univariate analysis absence of perineural and vascular invasion, stage, absence of lymph node infiltration and no need for transfusion were associated with improved overall survival. On multivariate analysis vascular invasion HR=3.137 (95%CI: 1.692-5.816; P = 0.0003) and postoperative complications HR=2.004 (95%CI: 1.198-3.354; P = 0.008) were identified as significant independent predictors of survival. The five-year survival rate was 18.9%, with five-year recurrence-free survival of 16.7%. CONCLUSION: Vascular invasion and postoperative complications were independent prognostic factors after curative resections of pancreatic cancer in studied cohort.

14 Article [Surgical therapy of pancreatic cancer - 5 years survival]. 2015

Loveček, M / Skalický, P / Klos, D / Neoral, Č / Ehrmann, J / Zapletalová, J / Švébišová, H / Yogeswara, T / Ghothim, M / Vrba, R / Havlík, R. · ·Rozhl Chir · Pubmed #26766155.

ABSTRACT: INTRODUCTION: The purpose was to identify 5-year survivors among a group of radically resected patients with pancreatic cancer and analyse the characteristics and factors associated with their 5-year survival. Single tertiary centre experience. METHOD: A prospectively maintained database of 155 pancreatic resections from January 2006 to June 2010 was scanned to identify patients after curative radical resections for pancreatic ductal adenocarcinoma. The clinical and pathological data was analysed retrospectively. The outcomes of the PDAC group were evaluated using Kaplan-Meier analysis (survival) with the Log-rank test and Cox regression analysis (evaluation of prognostic factors). Characteristics of the survivors were discussed. Significance level of 0.05 was used. Those factors were used as independent variables for Cox regression analysis whose significant effect on survival was shown based on Kaplan-Meier analysis. RESULTS: Among 155 patients undergoing a curative pancreatic resection, 73 had a pancreatic ductal adenocarcinoma. Fifteen patients (20.5%) after radical surgery survived over 5 years, 13 of whom are still alive. In the group of the survivors, the mean overall survival was 77.1 months (60110) and the median survival was 74 months. The mean relapse-free interval in the group of the survivors was 63.3 months (14110) with the median of 65 months. Factors associated with a longer survival included the absence of lymph node infiltration (p=0.031), uncomplicated postoperative course (p=0.025), absence of vascular invasion (p=0.017), no blood transfusions (p=0.015) and the use of postoperative therapy - predominantly chemotherapy (p=0.009). Significant independent predictors of survival included vascular invasion HR=2.239 (95%CI: 1.0934.590; p=0.028), postoperative chemotherapy HR=2.587 (95%CI: 1.3015.145; p=0.007) and blood transfusion HR=2.080 (95%CI: 1.0274.212; p=0.042). The risk of death was increased 2.2 times in patients with vascular invasion, 2.1 times in patients with transfusions, and finally 2.6 times in those with no chemotherapy. CONCLUSION: Factors associated with an improved overall survival included: the absence of lymph node infiltration, an uncomplicated postoperative course, absence of vascular invasion, no need of blood transfusions, and finally the use of postoperative chemotherapy. Vascular invasion, use of blood transfusions and postoperative adjuvant chemotherapy were significant independent prognostic factors of survival.

15 Article [Determination of CEA, EGFR and hTERT expression in peritoneal lavage in patients with pancreatic adenocarcinoma using RT - PCR method]. 2015

Ghothim, M / Srovnal, J / Bébarová, L / Tesaříková, J / Skalický, P / Klos, D / Prokopová, A / Vahalíková, M / Slavík, H / Vrbková, J / Neoral, Č / Havlík, R / Hajdúch, M / Loveček, M. · ·Rozhl Chir · Pubmed #26766154.

ABSTRACT: INTRODUCTION: The aim of this study is to assess the significance of CEA, EGFR and hTERT as markers of occult tumor cells for predicting treatment outcomes in pancreatic cancers, as well as determining the cut-off values of these markers individually in peritoneal lavage. METHOD: The study compared 87 patients undergoing palliative operations (bypass surgery, biological sampling for subsequent oncological treatment) for either stage III or IV (UICC) pancreatic ductal adenocarcinomas with a control group of 24 healthy patients. Abdominal cavity lavage was performed at the beginning of the surgery in both groups, using 100 ml of physiological solution (phosphate buffered saline, pH 7.2). The samples were transported in bottles containing 1.5 ml 0.5 M EDTA and 10 ml of fetal bovine serum. Total RNA samples were all processed and purified by reverse transcription. Occult tumor cells in the peritoneal lavage were detected by the real-time RT-PCR method using CEA, EGFR and hTERT as markers of tumor cells. Another aim was to calculate the cut-off values of these markers. Statistical analysis was done using software R (www.r-project.org) and Statistica (StatSoft, Inc. USA). RESULTS: Mean expression of CEA, EGFR and hTERT in peritoneal lavage in the control group was 2501, 716749 and 104 copies of mRNA / mg RNA. Threshold, cut-off values were determined as the "mean + 2 times standard deviation". Absolute expression values were further normalized to expression of the house-keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). After normalization, cut-off values of the tested markers were 4.89, 115.88 and 0.02 copies of mRNA/GAPDH mRNA. As regards absolute expression of the markers tested, only hTERT was able to statistically significantly (p<0.001) distinguish the analysed groups, where patients with advanced pancreatic adenocarcinoma had a higher expression of hTERT. Absolute expression of CEA or EGFR was not able to discriminate between the two groups. The more accurate normalized expression values of the test markers demonstrated a statistically significantly higher expression of hTERT (p<0.005) and CEA (p<0.001) in patients with advanced adenocarcinoma compared to the control group. CONCLUSION: Absolute hTERT expression in peritoneal lavage of patients with advanced pancreatic cancer was significantly higher compared to the control group.

16 Article [Synchronous cancer duplicities of pancreas and stomach/kidney and their surgical treatment]. 2015

Ghothim, M / Havlík, R / Skalický, P / Klos, D / Vrba, R / Strážnická, J / Skopal, L / Neoral, Č / Loveček, M. · ·Rozhl Chir · Pubmed #26174345.

ABSTRACT: INTRODUCTION: The occurence of synchronous pancreatic cancer and other primary cancer is not frequent and reaches about 5.6% as reported in autoptic studies. Double resections of the pancreas with another organ due to synchronous malignancies have been published only in quite sporadic sets of cases or individual case reports. The authors present three cases of synchronous pancreatic malignancies and stomach or renal cancers treated with surgery, including results and survival. CASES: Three patients with synchronous double cancer were identified in a series of 400 pancreatic resections (20062014). Two patients presented with symptoms of pancreatic periampullary tumors (bile duct obstruction, weight loss and abdominal pain). The second malignancies were identified as incidental during diagnostic work-up (asymptomatic cancer of the stomach, kidney). Pancreatoduodenectomies (PDE) with lymphadenectomies were performed due to ductal adenocarcinomas (pT2N1M0 G3 and pT3N1M0 G2). The second procedures included subtotal gastrectomy with lymphadenectomy (gastric adenocarcinoma pT1N1M0, G2) and nephrectomy (renal papillary carcinoma pT1bN0M0, G3). Postoperative adjuvant chemotherapy with gemcitabine was given in both patients. Survival rates were 12 and 19 months, respectively. The third patient suffered from abdominal pain and weight loss. Diagnostic work-up revealed stomach carcinoma and early pancreatic adenocarcinoma. Double resection - subtotal gastrectomy with lymphadenectomy and pancreatoduodenectomy with lymphadenectomy - was performed. Gastric adenocarcinoma pT2N2M0, G3 and pancreatic ductal papillary-mucinous adenocarcinoma pT2N0M0, G1 were found in the specimens. Adjuvant radiochemotherapy with 5-fluorouracil and leukovorine was given postoperatively. This patient is still alive nearly 5 years after the surgery, without any reccurence. CONCLUSION: The survival of patients with double synchronous pancreatic malignancies and other primary tumors in our set seems to be influenced by the stage and biology of pancreatic cancer. The survival was worse when the duplicity was presented with symptoms of pancreatic cancer. Pancreatic cancer found incidentally when another malignancy is presented has more favourable results.

17 Article [Pancreatic metastases--diagnosis, radical surgery, complications and survival]. 2015

Loveček, M / Skalický, P / Kliment, M / Klos, D / Ghothim, M / Vrba, R / Neoral, Č / Havlík, R. · ·Rozhl Chir · Pubmed #26112684.

ABSTRACT: INTRODUCTION: Although generally uncommon, pancreatic metastases are increasingly encountered in clinical practice. The benefit of pancreatic resections in this setting is unclear and still being discussed. Renal cell carcinoma is the most frequent primary tumour metastasing to the pancreas--R0 resections in cases of solitary metastases can be performed. Resections in malignant melanoma and ovarian cancer are rather considered as palliative. The aim of this study is to analyse our own set of patients operated on for metastases into the pancreas and evaluate the results of their surgical treatment. METHODS: We identified the patients operated on for metastases to the pancreas. Patient and tumour characteristics were summarized using descriptive statistics. RESULTS: A total of 9 patients (out of 312 patients undergoing resection for malignancy in the period of 2006-2014) with pancreatic metastases were analysed. All but one were asymptomatic; the symptomatic patient suffered from GI bleeding. All patients had a metachronous lesion with a median length of 12 years (421 years) between the initial operation and pancreatic resection. The most common metastasing tumour was renal cell carcinoma (77%) with the highest incidence occurring at the head of the pancreas (44%). The most frequent procedure used was the pylorus-preserving pancreatic head resection (44%). The median operating time was 247 min, (126375 min). Six patients were complication free, the median of their hospital stay was 9.5 days (812 days). Complications included PPH type C and PF type B both of which required surgical intervention; however, PF type A required no intervention. No postoperative deaths occurred, multiple metastases were found in 4 patients with renal cell carcinoma metastases. The median of follow-up has been 11.5 months, (334 months). CONCLUSION: Survival after pancreatic resections due to renal cell carcinoma is favourable. Mortality is low and morbidity is similar to that associated with pancreatic resections due to other aetiologies, making surgery a valid and safe treatment option. Lifelong follow-up of patients after nephrectomy is advised. Resections in pancreatic metastases of malignant melanoma or ovarian carcinoma are considered as palliative, their indication being individual following interdisciplinary consultation.

18 Article Mitochondrial changes in adenocarcinoma of the pancreas. 2013

Novotný, Radko / Ehrmann, Jiří / Tozzi di Angelo, Igor / Procházka, Vlastimil / Klos, Dušan / Loveček, Martin / Kysučan, Jiří / Havlík, Roman. ·Laboratory of Microscopic Methods, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc, Czech Republic. rnovot@centrum.cz ·Ultrastruct Pathol · Pubmed #23650995.

ABSTRACT: The aim of our study was to analyse the mitochondrial ultrastructure in primary ductal adenocarcinomas of the pancreas and to compare it with normal pancreatic cells. 52 samples of adenocarcinoma of the pancreas obtained by surgical resection or by endosonographic biopsy were examined. Compared to normal mitochondrial ultrastructure in non-tumorous cells, the mitochondria in cancer cells had a dense matrix and condensed configuration or with lucent-swelling matrix associated with disarrangement and distortion of cristae and partial or total cristolysis. Functionally, these structural alterations presume the presence of hypoxia-tolerant and hypoxia-sensitive cancer cells.

19 Article Occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic cancer. 2013

Havlik, Roman / Srovnal, Josef / Klos, Dusan / Benedikova, Andrea / Lovecek, Martin / Ghothim, Mohamed / Cahova, Dana / Neoral, Cestmir / Hajduch, Marian. ·Department of Surgery I, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic. ·Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub · Pubmed #23128819.

ABSTRACT: AIMS: The aim of this study was to test the hypothesis that occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic adenocarcinoma. METHODS: Real-time RT-PCR analysis of CEA, EGFR and hTERT transcript levels was used to identify occult tumour cells in peritoneal lavage samples from 96 pancreatic cancer patients. RESULTS: We found significant association between CEA expression levels in peritoneal lavage and clinical stage. We also found that EGFR transcript levels were higher in peritoneal lavage samples from patients with high grade tumours than in samples from patients with low grade tumours. Detection of CEA and/or EGFR occult tumour cell markers in the peritoneal lavage was associated with significantly shorter overall survival and increased hazard ratio for disease recurrence. CONCLUSIONS: The results show that the presence of occult tumour cells in peritoneal lavage is a negative prognostic factor for survival in pancreatic cancer patients, and that detection of occult tumour cells using PCR-based methods can identify patients with advanced disease for whom radical surgery is likely to have little benefit.

20 Article [The importance of endosonography in preoperative management of patients with pancreatic head carcinoma]. 2012

Loveček, M / Kliment, M / Skalický, P / Klos, D / Angelo, I Tozzi Di / Kovala, P / Havlík, R. ·Chirurgicka Klinika FN a LF UP Olomouc. mlovecek@seznam.cz ·Rozhl Chir · Pubmed #23301680.

ABSTRACT: INTRODUCTION: Pancreatic ductal cancer remains a devastating disease with an urgent need for improved diagnostics and new treatment strategies. It has no early specific symptoms, shows rapid progression and is practically undiagnosable in the early stage. Survival of radically operated patients is rather unsatisfactory. Nonetheless, only radical surgical resection offers potentially curative treatment. MATERIAL AND METHODS: The authors present a set of 70 patients (2009-2011) who underwent radical surgery - pancreatic head resection - for ductal pancreatic head adenocarcinoma. A retrospective study analyzes the accuracy of T-staging using preoperative CT and EUS. RESULTS: In 21 (30%) patients, CT did not prove pathology in the head of the pancreas. Subsequent endosonography revealed a mass in the head of the pancreas in 88% of patients with negative CT scans. The conformity of CT (detection of the mass) with the histopathological finding was detected in 68.2% of cases, 95% CI for compliance: 55.6%-79.1%. The conformity of endosonography (detection of the mass) with the histopathological finding was detected in 96.0% of cases, 95% CI for compliance: 86.3%-99.5%. The conformity between CT and endosonography was found in 68.8% of cases, 95% CI for compliance: 53.8%-81.3%. The conformity of preoperative CT staging and final histopathological staging was observed in 18.2% of cases, 95% CI for compliance: 9.8%-29.6%. The conformity of preoperative endosonography staging and final histopathological staging was seen in 42.0% of cases, 95% CI for compliance: 28.2%-56.8%. The conformity of accuracy of preoperative CT staging and endosonography staging was detected in 37.5% of cases, 95% CI for compliance: 23.9%-52.7%. In 58.3% of cases, endosonography compared with CT findings evaluated higher T stage (p = 0.001). CONCLUSION: Pancreatic head carcinoma presents mostly with obstructive jaundice. CT diagnosis of small tumours often fails. Subsequent endosonography in case of a negative CT usually contributes significantly to the final diagnosis and helps determine the indication for surgery. EUS is more accurate than CT in showing the tumour mass in the pancreatic head. In our group EUS revealed the mass in 96% of patients versus 68% in CT. When evaluating the staging, CT is accurate only in 18.2% of patients, EUS in 42% of patients. Both methods, EUS and particularly CT, underestimate the actual final T-staging of the disease.

21 Article [Quality of life is an important factor in the indication in patients with advanced pancreatic carcinoma--a prospective multicentric study]. 2012

Ryska, M / Dusek, L / Pohnán, R / Bunganic, B / Bieberová, L / Ryska, O / Lovecek, M / Jon, B / Rupert, K / Krejcí, M / Jarkovský, J. ·Chirurgická klinika 2. LF UK a UVN Praha. miroslav.ryska@uvn.cz ·Rozhl Chir · Pubmed #22880267.

ABSTRACT: INTRODUCTION: The aim of this report is to present results of prospective multicentric study on quality of life (QoL) in advanced ductal pancreatic adenocarcinoma patients. MATERIAL AND METHOD: In 426 patients with advanced ductal pancreatic adenocarcinoma, the following parameters were studied: type of treatment, complication rates, 1, 2 and 3-year survival rates. QoL was assessed in 151 patients, using a generic SF-36 questionnaire prior the therapy and then 3 months after the treatment. Arithmetic mean and standard deviation (SD) were used for the QoL pool analysis. The results were evaluated using SF-36 software, t-test for independent samples, ANOVA, paired t-test and SPSS 19.0.1 (IBM Corporation, 2010). The p value < 0.05 was considered as statistically significant. RESULTS: There was a significant difference in the median, 1,2 and 3-year survival rates in the patients with stage III pancreatic cancer who underwent radical resection (RR) compared to the paliative therapy patients (p < 0.001). The highest initial overal QoL value was observed in 39 stage III patients who underwent RR (60.5 +/- 1.84) and no significant decrease in this value was recorded over a 3-month postoperative period (difference--5.1 +/- 16.6, p = 0.064). Paliative therapy resulted in significant reduction in the overall QoL value (p = 0.020). In the paliative therapy group of patients, BDA resulted in significant reduction in the overall QoL value 3 months after the procedure (p = 0.017 vs. ns.). In the group of stage IV patients, nonsignificant increase in the overall QoL value was recorded in 8 patients 3 months after BDA (46.4 +/- 17.0 vs. 51.1 +/- 9.5 p = 0.525). Nonsignificant increase in the overal QoL values was also observed in 18 patients after stent introduction (30.6 +/- 8.3 vs. 31.5 +/- 8.5 p = 0.783). Nonsignificant deterioration in QoL was recorded in patients undergoing exploration, whose initial QoL values corresponded with those in RR patients, while 3 months after the explorative surgery their QoL values were similar to those recorded in the stent group patients (62.0 +/- 16.1 vs. 41.7 +/- 23.6 s rozdílem -20.3 +/- 16.2 p < 0.001). CONCLUSION: Based on the results of the multicentric prospective study in patients with locally advanced stage III and IV ductal pancreatic adenocarcinoma, the following conclusions can be presented: (1) median and 1, 2 and 3-year survival rates in stage III patients were significantly higher in the RR group compared to the paliative therapy patients, (2) initial QoL in stage III patients was significantly the highest in patients who underwent RR. Significant decrease in QoL was recorded in BDA patients. Paliative stent introduction resulted in nonsignificant improvement in the QoL 3 months after the procedure, while the initial QoL values were the lowest in this group, (3) QoL assessment in stage IV patients showed statistically nonsignificant improvement after BDA or stent procedures, the most significant deterioration was observed in the exploration group, (4) no complication which would result in prolongation of the respective hospitalization times was recorded in 67%, (5) early postoperative complications did not result in significant QoL deterioration 3 months after the procedure, (6) absence of chemotherapy results in significant decrease in QoL.

22 Article [Pancreatic cancer surgery at Ist Surgical Clinic of the Olomouc Faculty Hospital (FN Olomouc)]. 2010

Lovecek, M / Neoral, C / Klos, D / Skalický, P / Kysucan, J / Vrba, R / Melichar, B / Svébisová, H / Tozzi di Angelo, I / Kliment, M / Havlík, R. ·I. Chirurgická klinika LF UP a FN Olomouc. ·Rozhl Chir · Pubmed #21404512.

ABSTRACT: INTRODUCTION: Surgical treatment plays a key role in the efforts to improve prognosis of patients with pancreatic cancer. The pancreatic cancer incidence rates are on increase and so does the number of patients undergoing potentially curative resection procedures. However, despite all diagnostic advancements and treatments adjusted to specific patient's needs, the outcomes are not satisfactory enough. The aim of the surgical procedure is to radically remove the tumor, including the regional lymph nodes, to promote early and uncomplicated healing and to facilitate early initiation of oncological treatment. AIM: The aim of the study was to assess current potential of diagnostic and surgical treatment in pancreatic cancer when all currently available diagnostic methods are emloyed and to present the university clinic's outcomes. METHODS AND PATIENT GROUP: From 2006 to IX 2010, a total of 177 pancreatic resections and 123 right-sided pancreatoduodenectomies for malignant disorders were performed at the authors' clinic. 76 pancreatoduodenectomies were performed for ductal carcinoma of the pancreatic head. The study group included 51 males and 25 females, the mean age of 62.9 years. Based on the TNM classification (UICC), 11% of the subjects presented with stage I, 78% with stage II and 3% with stage III diseases. The procedures radicality was the following: R0 in 59 subjects, R1 in 5 subjects while in 12 subjects, the radicality was undetected by the authors. Histopatological grading in this patient group was as follows: G1 in 20%, G2 in 34% and G3 in 46% of the subjects. Perineural invasion, invasion into lymphatic vessels or other vessels was not detected in 21 subjects (27.6%). The authors assessed complication rates based on the DeOliveira classification and survival rates in individual disease stages. OUTCOMES: Complications occurred in 44.7% of the operated subjects. Serious complications requiring reintervention were reported in 13 subjects (17.1%), including reinterventions in general anesthesia in 10 subjects (13.1%). Two patients died: a 79-year old female died from multiorgan failure as a result of aspiration, and a 76-year old male died from multiorgan failure following completion of pancreatectomy due to pancreaticojejunal anastomosis insufficiency. The thirty- and sixty-day mortality rate was 2.6%, however, it was null over the past three years. The mean survival time was 17.1 months, with the median of 13.5 months. The patient group's overall 3-, 6-, 9-, 12, 15- and 18- month survival following radical resections was 95.6%, 90.3%, 76.3%, 62.7%, 52.3% and 45%, respectively. 82%, 52%, 35% and 35% of the operated stage I patients survived 1, 2, 3 and 4 years, respectively. The mean hospitalization duration was 16.8 days (10-45). CONCLUSION: Although the procedures are extremely demanding, especially in the reconstruction phase, the outcomes have improved significantly due to ongoing experience, improvements in the surgical technique and in the complex postoperative care. At specialized clinics, the mortality rate has dropped below 5%, the morbidity rate below 40% and the postoperative dehiscence rates below 10%. During the past three years, the authors' clinic has reached null 30- and 60-day mortality rate following the pancreatic head resections, the complication rate following pancreaticoduodenal anastomosis is slightly above 5% (6.5%) and the morbidity rate is slightly above 40% (44.7%). The authors consider the procedure safe at their clinic and all indicated patients are expected to benefit from it.

23 Article [Benefit of PET/CT in the preoperative staging in pancreatic carcinomas]. 2010

Kysucan, J / Lovecek, M / Klos, D / Tozzi, I / Koranda, P / Buriánková, E / Neoral, C / Havlík, R. ·Chirurgická klinika FN a UP Olomouc. ji.k@email.cz ·Rozhl Chir · Pubmed #20925260.

ABSTRACT: OBJECTIVE: Prognosis of patients with pancreatic cancer is poor. Median survival from diagnosis without determining surgical treatment is 3-11 months, after surgical treatment between 13-20 months according to various studies. 5-year survival rate is below 5%. The only chance of cure remains a radical surgical resection. Early diagnosis and determining resectability of tumour is the most important objective in patients with pancreatic cancer. Aim of this work is to evaluate the benefits and define the role of 18F-FDG PET/CT in preoperative staging. MATERIAL AND METHODS: 195 patients (103 men, 92 women, mean age 66.7 year, range 32-88 years) with suspected pancreatic lesions underwent enhanced 18F-FDG PET/CT in the preoperative staging in addition to standard investigative methods (ultrasonography, contrast enhanced CT, EUS, EUS FNA). All PET/CT findings were compared with standard methods (CT, EUS, EUS FNA), with peroperative findings and definitive histology in surgical patients as the reference standards. Interpretation of the extent of the tumor defined by TNM classification. Limitations of the local resectability was advanced local stage (T4) and presence of distant metastases (M1). RESULTS: In 195 patients with suspected pancreatic lesions was pre-operatively performed PET/CT in the period 1/2007-3/2009. 153 patients with pancreatic cancer, of which 72 was not suitable for radical surgery because of local inoperability or a generalization of the disease. The sensitivity of PET/CT in the capture of primary lesions was 92.2%, specificity 90.5%. False negative findings in 12 patients, false-positive results occurred in 4 cases, positive predictive value (PPV) 97.2%, negative predictive value (NPV) 76.0%. In the assessment of regional lymph nodes sensitivity was 51.9%, specificity 58.3%, PPV 58.3%,NPV 51.9%. In detection of distant metastases PET/CT reached sensitivity 82.8%, specificity 97.8%, PPV 96.9%, NPV 87.0%. PET/CT found distant metastases in 12 patients, which standard methods failed to detect. Surgery was cancelled in 15 patients (15.6%) with potentially resectable tumour based on the performance of PET/CT findings and the management of treatment was changed. CONCLUSION: PET/CT is highly sensitive and specific method suitable for preoperative staging of pancreatic cancer. It improves the selection of patients for surgery, who can benefit from and reduces the number of incorrectly indicated operations.

24 Article [Possibility of using the determination of minimal residual disease in pancreatic adenocarcinoma using real-time RT-PCR--a pilot study]. 2010

Klos, Dusan / Lovecek, Martin / Srovnal, Josef / Benedíková, Andrea / Růzková, Vera / Radová, Lenka / Hajdúch, Marián / Neoral, Cestmír / Havlík, Roman. ·Univerzita Palackého v Olomouci, Lékarská fakulta, I. chirurgická klinika FN. dklos@seznam.cz ·Cas Lek Cesk · Pubmed #20662469.

ABSTRACT: BACKGROUND: Minimal residual disease in patients with pancreatic cancer is defined as the presence of isolated tumor cells in the patient's body, in which the primary tumor was removed and is currently without clinical signs of disease. These isolated tumor cells may be described as precursors of micrometastases. Assessment of MRD in patients with this highly malignant disease could eliminate burdensome implementation of surgery in patients with systematic dissemination of molecular disease and provide a more precise prognosis. METHODS AND RESULTS; The study to date included 70 patients operated on with curative intent for carcinoma of the pancreas. Samples of peripheral and portal blood, bone marrow, peritoneal lavage and of the tumor itself were analyzed by real-time PCR which measured the expression of hTERT (telomerase), EGFR1 (receptor for epidermal growth factor) and CEA (carcinoembryonic antigen). The expression of these markers was correlated with clinicopathological characteristics and survival parameters. We found a statistically significant association between EGFR expression levels in the portal blood and clinical stage--patients with advanced disease have a higher expression of EGFR in the portal stream and peritoneal lavage in contrast to patients without the presence of metastases. CONCLUSIONS: The results of this pilot study demonstrated a high sensitivity and specificity of the RT-PCR method for detecting circulating tumor cells in patients with pancreatic cancer. By utilizing this methodology, we are able to provide prognostic value of minimal residual disease and its significance for the indication of radical surgery for pancreatic cancer.

25 Article Endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: the utility and impact on management of patients. 2010

Kliment, Martin / Urban, Ondrej / Cegan, Martin / Fojtik, Petr / Falt, Premysl / Dvorackova, Jana / Lovecek, Martin / Straka, Martin / Jaluvka, Frantisek. ·Department of Gastroenterology, Hospital Vitkovice, Ostrava, Czech Republic. martin.kliment@nemvitkovice.cz ·Scand J Gastroenterol · Pubmed #20626304.

ABSTRACT: OBJECTIVE: It is controversial whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is beneficial in all patients with suspected pancreatic cancer. The aim of this study was to assess diagnostic yield, safety and impact of EUS-FNA on management of patients with solid pancreatic mass. MATERIAL AND METHODS: Consecutive patients undergoing EUS-FNA of solid pancreatic mass were enrolled. Gold standard for final diagnosis included histology from surgical resection. In patients without surgery, clinical evaluation methods and repeated imaging studies were used for the comparison of initial cytology and final diagnosis. Patients were followed-up prospectively focusing on subsequent treatment. RESULTS: Among 207 enrolled patients, final diagnosis was malignant in 163 (78.6%) and benign in 44 (21.4%). The sensitivity, specificity and accuracy of EUS-FNA in diagnosing pancreatic cancer were 92.6% (95% CI: 87.20-95.96), 88.6% (95% CI: 74.64-95.64) and 91.8% (95% CI: 87.24-94.81), respectively. No major and five (2.4%) minor complications occurred. Of 151 true-positive patients by EUS-FNA, 57 (37.7%) were surgically explored, of whom 28 (49.1%) underwent resection. Ten of 12 patients with false-negative cytology were explored based on detection of mass on EUS, of whom two had a delay due to false-negative cytology without curative treatment. From the whole study cohort, EUS-FNA had positive and negative impacts on subsequent management in 136 (65.7%) and 2 (0.9%) patients, respectively. CONCLUSIONS: EUS-FNA provides accurate diagnosis in 92% and has positive therapeutic impact in two-thirds of patients with solid pancreatic mass. Despite negative cytology, surgical exploration is recommended in clinical suspicion for pancreatic cancer and solid mass on EUS.

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