Zdeněk Kala

Masaryk University

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Vladimír Procházka

Masaryk University

Lumír Kunovský

Masaryk Memorial Cancer Institute

Jiří Dolina

University Hospital Brno

Filip Marek

Masaryk University

Jan Hlavsa

Masaryk University

Petr Kysela

Masaryk University

Tomáš Andrašina

University Hospital Brno

Ondřej Slabý

Central European Institute of Technology

Radek Kroupa

Masaryk University

Igor Penka

Masaryk University

Cooperative Institutions

University of Birmingham

569

NIHR Birmingham Biomedical Research Centre

453

ESCP Business School

369

ESCP Business School

360

National University of Avellaneda

354

Masaryk University

272

University Hospital Brno

207

Charles University

123

Collaborative Group (United States)

Yorkshire Cancer Research

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Gastroezofageální refluxní choroba a variabilita v genech proCDX2 a receptor vitaminu D

Simona Valová Petra Bořilová Linhartová Tereza Deissová Filip Marek Jiří Dolina

Nase výsledky naznacuji, že polymorfizmy v genech pro CDX2 a vitamin D receptor mohou ovlivňovat riziko rozvoje refluxni ezofagitidy a/nebo Barretova jicnu u pacientů s gastroezofagealni refluxni chorobou.

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[Solid pseudopapillary tumor of the pancreas: 5 case reports].

PubMed (2004)

Jan Brázdil Markéta Hermanová Leoš Křen Zdeněk Kala Christian Neumann

Solid pseudopapillary tumor of pancreas belongs to rare tumors of exocrine pancreas, which typically affects young women. In a retrospective study the authors reviewed their experience obtained with five cases of this tumor from 1994 until the present time. The group included four women (from 16 to 47 years, mean age 25 years) and one man (43 years old). Clinical symptoms were characterized by abdominal pain in three cases, two years lasting domed belly and an incidental finding in another case. The palpation examination of epigastrium revealed a palpable tumor, visible in sonographic examination and CT. All patients underwent surgical resection of the tumor. The tumor affected cauda of the pancreas (pancreatic tail) in four cases and head of the pancreas in one case. Histopathological examination established the diagnosis of solid pseudopapillary tumor of pancreas in four cases and solid pseudopapillary carcinoma in one case. A typical immunophenotype of tumorous cells was demonstrated and in four cases there was positivity of progesterone receptor. The progesterone and estrogen receptors were negative in the male patient. Solid pseudopapillary tumor of pancreas is the tumor of low malignancy with excellent prognosis. Correct diagnosis and surgical removal of the tumor results in curing up in most cases.

Palpation

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Intraoperative oesophageal manometry with new calibration tubeduring the laparoscopic antireflux surgery

Vladimír Procházka Filip Marek Zdeněk Kala Jiří Dolina

Number of probe dislocations was significantly lower in the newly designed calibration probe. Aside of lowering the risk of injury to the oesophagus and easier manipulation, the desired influence of the new device on the postoperative dysphagia occurrence has to be revalued on a higher number of patients, so the study continues.

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Pokroky v minimálně invazivní péčbě chorob trávicího traktu

Zdeněk Kala

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Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Frontiers in Oncology (2021)

Ye Lu Manuel Gentiluomo Angelica Macauda Domenica Gioffreda Maria Gazouli

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10 −5 ) compared with the additive effects (p>10 −3 ), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10 −8 ). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Genome-wide Association Study

Genetic Association

genetic model

10.3389/fonc.2021.771312

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Differences in Transcript Levels of ABC Transporters Between Pancreatic Adenocarcinoma and Nonneoplastic Tissues

Pancreas (2013)

Beatrice Mohelníková-Duchoňová Veronika Brynychová Martin Oliverius Eva Honsová Zdeněk Kala

The aim of this study was to evaluate transcript levels of all 49 human ATP-binding cassette transporters (ABCs) in one of the most drug-resistant cancers, namely, the pancreatic ductal adenocarcinoma (PDAC). Association of ABCs levels with clinical-pathologic characteristics and KRAS mutation status was followed as well.Tumors and adjacent nonneoplastic tissues were obtained from 32 histologically verified PDAC patients. The transcript profile of ABCs was assessed using quantitative real-time polymerase chain reaction with a relative standard curve. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing.Most ABCs were deregulated in PDAC and 10 ABCs were associated with clinical-pathologic characteristics. KRAS mutations did not change the global expression profile of ABCs.The expression of ABC transporters was significantly deregulated in PDAC tumors when compared to nonmalignant tissues. The observed up-regulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2 in tumors may contribute to the generally poor treatment response of PDAC. The up-regulation of ABCA1, ABCA7, and ABCG1 implicates a serious impairment of cellular cholesterol homeostasis in PDAC. On the other hand, the observed down-regulation of ABCA3, ABCC6, ABCC7, and ABCC8 suggests a possible role of stem cells in the development and progression of PDAC.

ABCG1

Abcg2

ABCC1

10.1097/mpa.0b013e318279b861

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[Radiofrequency ablation of pancreatic neuroendocrine tumor].

PubMed (2011)

Jan Hlavsa Vladimír Procházka Zdeněk Kala Martin Man Tomáš Andrašina

Pancreatic neuroendocrine tumors (PNETs) include a broad range of neoplasms spanning from relatively benign to malignant. Radical resection has been advocated as the only curative method. Debulking (R2) resection can be indicated for locally unresectable PNETs. Debulking surgery improves the quality of life and prolongs overall survival. The disadvantages of this approach include bleeding, pancreatic fistula and tumor spread. No alternative method that would eliminate these complications has been published yet. Considering the encouraging results of the studies describing radiofrequency ablation (RFA) of locally advanced pancreatic cancer, a question arises, whether it might be possible to use RFA as a R2 resection alternative in PNETs.A 73-year-old gentleman had been admitted due to abdominal pain and hyperglycaemic syndrome. Contrast-enhanced CT showed a tumor of pancreatic head invading portal vein (PV) and superior mesenteric vein (VMS). A surgery was indicated on the basis of EUS-guided FNAB that verified a PNET of uncertain biological behaviour. The surgery confirmed a locally advanced tumor of pancreatic head invading the PV and SMV. Due to the polymorbidity, radical pancreatoduodenectomy with SMV resection was not indicated. Because of the presence of symptoms, RFA of the PNET using ValleyLab generator with cooltip cluster electrode, was performed. Postoperative course was uneventful. Final immunohistochemical examination verified a well-differentiated grade 1 PNET. The patient was regularly monitored during a three-year follow-up. The quality of life was evaluated using standardized EORT QLQ-30 questionnaire. Pain was assessed by a ten-point visual analogue scale (VAS). Ablated area was evaluated annually by contrast-enhanced CT. Postoperatively, abdominal pain ceased (pain decrease from 2 to 0 on VAS). Insulin dose was reduced from 46 IU (international units) to 20 IU of Humulin-R per day. CT verified tumor regression according to RECIST (response evaluation criteria in solid tumors). During the three-year follow-up, no local progression or tumor dissemination was observed.We present the first case report of a patient with locally advanced symptomatic pancreatic neuroendocrine tumor successfully treated by intraoperative radiofrequency ablation. More clinical studies are needed to evaluate the clinical relevance of this cytoreductive method in the PNET indication.

Debulking

Pancreatic tumor

Superior mesenteric vein

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Multiple neuroendocrine tumor of the small bowel: a case report and a review of literature

Vnitřní lékařství (2018)

Lumír Kunovský Milan Dastych Oldřich Robek Roman Svatoň Jakub Vlažný

Maligní tumory tenkého střeva tvoří jen asi 1-2 % ze všech nádorů gastrointestinálního traktu. Ačkoli neuroendokrinní tumory (NETs) jsou relativně vzácné, tak i přesto představují druhou nejčastější malignitu tenkého střeva (hned po adenokarcinomu). Klinicky se projevují bolestí břicha, střevní obstrukcí, průjmy, úbytkem na váze či krvácením. Diferenciální diagnostika skrytého gastrointestinálního krvácení může být někdy výzvou jak pro metody endoskopické, tak radiologické. Prezentujeme případ 80letého pacienta došetřovaného pro těžkou mikrocytární anémii. Základní endoskopické metody neobjasnily zdroj skrytého krvácení. Nakonec pomocí kapslové endoskopie (CE) byla diagnostikována izolovaná ulcerace ilea s navalitými okraji. CT enterografie nezachytila žádnou další lézi. Vzhledem k pozitivním hodnotám chromograninu A, nálezu na endoskopických a zobrazovacích metodách bylo vysloveno podezření na NET tenkého střeva. Během operace bylo zjištěno 7 ložisek NET tenkého střeva a byla provedena resekce 120 cm ilea. Dle definitivní histologie bylo v preparátu nalezeno celkem 15 ložisek NET grade 1. Kontrolní octreoscan neodhalil žádné další reziduální ložisko. Představujeme případ pacienta s celkem 15 ložisky NET tenkého střeva diagnostikovaného pomocí CE s následnou úspěšnou resekcí ilea.

10.36290/vnl.2018.135

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Možnosti miniinvazivní chirurgie u pacientů s Crohnovu nemocí a ulcerózní kolitidou

Gastroenterologie a hepatologie (2017)

Lumír Kunovský Filip Marek Zdeněk Kala Jiří Dolina Petr Moravčík

Crohnova nemoc a ulcerozni kolitida jsou řazeny mezi chronicka zanětliva onemocněni střev, u kterých ma i v době možnosti biologicke terapie chirurgicka lecba stale nezastupitelne misto. V clanku jsou strucně shrnuty indikace k operacnimu řeseni u pacientů s idiopatickými střevnimi zaněty. Dale se zaměřujeme na možnosti miniinvazivnich operacnich technik od laparoskopicky asistovaných výkonů po relativně nove miniinvazivni metody. V textu jsou zminěny nase zkusenosti - výhody ci uskali nově zavaděných operacnich technik s odkazem na nejnovějsi soucasne studie a literaturu. Rozebran je take vliv chirurgicke lecby na kvalitu života u pacientů s nespecifickými střevnimi zaněty.

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Abstract 4976: Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection

Cancer Research (2018)

Natalia Gabło Vladimír Procházka Táňa Macháčková Eva Vencovska Zdeněk Kala

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer, associated with limited treatment options and high mortality rates. Radical resection remains the most effective curative approach for patients in early stage of disease. However, there is a high risk of surgical morbidity/mortality, and therefore development of prognostic assays to identify those patients who will not benefit from surgical resection, present important unmet medical need. miRNAs are small, non-coding RNAs, that post-transcriptionally regulate gene expression. miRNAs are frequently deregulated under pathological conditions including PDAC and therefore present promising candidates for new prognostic biomarkers in PDAC. Materials and methods: We analyzed preoperative plasma samples obtained from 45 PDAC patients who underwent radical tumor resection. Patients were divided into two prognostic groups: 23 patients with poor prognosis (median overall survival (OS) = 10 months) and 22 patients with good prognosis (median OS = 25 months). cDNA libraries were prepared using CleanTaq Small RNA Library Prep Kit (TriLink). The sequencing analysis were performed by Next 500/550 High Output v2 Kit - 75 cycles using the NextSeq 500 instrument (both Illumina). For miRNA mapping and analysis, an online tool Chimira was used. Obtained data were statistically evaluated using the Bioconductor edgeR and DESeq2 package. Results: When miRNA expression profiles of the patients from good and poor prognostic group were compared, 41 miRNAs were identified to have significantly different plasma levels between the two groups (P<0.05). Out of these miRNAs, 33 were found to have significantly higher levels in plasma samples of patients with poor prognosis (e.g. mir-376a-3p, mir-6763-5p, mir-885-3p, mir-1258, mir-192-5p, mir-6751-5p, mir-891a-5p, mir-3178, mir-3173-3p, mir-378g, mir-4453, mir-6764-5p, mir-556-5p, mir-6836-5p, mir-6516-5p), and 8 miRNAs have lower levels (mir-885-3p, mir-192-5p, mir-3178, mir-8072, mir-378d, mir-99a-5p, mir-30a-5p, mir-1976) compared to those with good prognosis. Conclusion: Our findings suggest, that there is a blood plasma miRNAs signature associated with the prognosis of PDAC patients, and after independent validation, miRNAs from this signature may allow for a prognostic stratification of PDAC patients. This work was supported by Ministry of Health of the Czech Republic, grant nr.15-33158A, 15-34553A, 15-31627A, 15-34678A, 16-31314A, 16-31765A and by grant of Czech Grant Agency nr. 16-18257S. Citation Format: Natalia Gablo, Vladimir Prochazka, Tana Machackova, Eva Vencovska, Zdenek Kala, Jiri Sana, Parwez Ahmad, Jaroslav Juracek, Marek Vecera, Marek Svoboda, Ondrej Slaby. Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4976.

10.1158/1538-7445.am2018-4976

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