Genes carrying high-penetrance germline mutations may also be associated with cancer susceptibility through common low-penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high-penetrance PDAC-associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B-AS1/ANRIL, showed a genome-wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07-1.15, P = 5.25 × 10-9 ). CDKN2B-AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.

• MeSH
• duktální karcinom pankreatu * genetika   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nádory slinivky břišní * genetika   MeSH
• RNA dlouhá nekódující * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: This study aimed to validate the accuracy of the Preoperative Pancreatic Resection (PREPARE) risk score in pancreatic resection patients. PATIENTS AND METHODS: This prospective study included 216 patients who underwent pancreatic resection between January 2015 and December 2018. All patients in our cohort with weight loss or lack of appetite received dietary advice and preoperative oral nutritional supplementation (600 kcal/day). Demographic, clinicopathological, operative, and postoperative data were collected prospectively. The PREPARE score and the predicted risk of major complications were computed for each patient. Differences in major postoperative complications were analyzed using a multivariate Cox proportional hazards regression model. The predicted and observed risks of major complications were tested using the C-statistic. RESULTS: The study included 216 patients [117 men (54.2%)] with a median age of 65.0 (30.0-83.0) years. The majority of patients were classified as American Society of Anesthesiologists (ASA)' Physical Status score II (N = 164/216; 75.9%) and as "low risk" PREPARE score (N = 185/216; 85.6%) before the surgery. Only 4 (1.9%) patients were malnourished, with albumin levels of less than 3.5 g/dl. The most common type of pancreatic resection was a pylorus-preserving pancreaticoduodenectomy (N = 122/216; 56.5%). Major morbidity and 30-day mortality rates were 11.1% and 1.9%, respectively. The type of surgical procedure (hazard ratio [HR]: 3.849; 95% confidence interval [CI]: 1.208-12.264) and ASA score (HR: 3.089; 95% CI: 1.067-8.947) were significantly associated with the incidence of major postoperative complications in multivariate analysis. The receiver operating characteristic curve was 0.657 for incremental values and 0.559 for risk categories, indicating a weak predictive model. CONCLUSION: The results of the present study suggest that the PREPARE risk score has low accuracy in predicting the risk of major complications in patients with consistent preoperative nutritional support. This limits the use of PREPARE risk score in future preoperative clinical routines.

• Publikační typ
• časopisecké články MeSH

Úvod: Robotická chirurgie slinivky břišní dosud není v České republice výrazně rozšířena. V celosvětovém měřítku je postupně, zejména v high-volume centrech, systematicky implementována. Studie prezentuje první zkušenosti s robotickou operativou slinivky břišní v pankreatochirurgickém high-volume centru v ČR. Metody: Srovnávací analýza první desítky pacientů operovaných roboticky pro patologii na slinivce břišní se srovnatelným souborem operovaných otevřeně (výkony menšího rozsahu: levostranná pankreatektomie s/bez splenektomie, enukleace, centrální resekce) hodnotí věk, délku hospitalizace, pobyt na JIP, krevní ztráty a operační čas pomocí neparametrického Mann-Whitneyova U-testu, a komplikace a rehospitalizace pomocí deskriptivní statistiky. Výsledky: Srovnávané soubory tvoří 10 pacientů (5 žen) s provedeným robotickým výkonem (5× enukleace, 4× distální pankreatektomie a centrální resekce – medián věku 65,3 [46–76] let) a 10 pacientů (5 žen) se srovnatelnými otevřenými výkony (5× enukleace, 4× distální resekce a centrální resekce – medián věku 65,5 [52–78] let). Délka hospitalizace 4,5 vs. 9 dnů (p = 0,0003) a délka operace 275 vs. 142 min (p = 0,004) byly statisticky rozdílné u robotické vs. otevřené skupiny. Pobyt na JIP a krevní ztráty byly nižší ve skupině robotické, ale ne statisticky významné, věk byl srovnatelný. Komplikace podle Clavien-Dindovy klasifikace ve skupině otevřené: 3× typ II, 1× typ IIIa, 1× typ IIIb, ve skupině robotické 1× typ II a 1× typ IIIa. Rehospitalizace v souboru otevřených byla 2×, v souboru robotických 1×, vždy pro pozdní pooperační komplikaci. Závěr: Robotická chirurgie slinivky břišní je v současnosti v ČR v úplných začátcích. Dosavadní zkušenost s první desítkou nemocných operovaných prostřednictvím robotického systému DaVinci Xi přinášejí slibné výsledky v podobě zkrácení hospitalizace, ale za cenu delšího operačního času.

Introduction: Robotic pancreatic surgery is still not widely used in the Czech Republic. On a global scale, it is gradually being systematically implemented, especially in high-volume centers. The study presents the first experiences with robotic pancreatic surgery in a pancreatic surgery high-volume center in the Czech Republic. Methods: Comparative analysis of the first ten patients operated on robotically for pancreatic pathology with a comparable group operated open (smaller procedures: left pancreatectomy with/without splenectomy, enucleation, central resection) evaluates age, length of hospitalization, ICU stay, blood loss and operative time using non-parametric Mann--Whitney U-test, and complications and rehospitalization using descriptive statistics. The results: The compared sets consist of 10 patients, 5 women, with a robotic procedure (5× enucleation, 4× distal pancreatectomy and central resection – median age 65.3 [46–76] years) and 10 patients, 5 women, with comparable open procedures (5× enucleation, 4× distal resection and central resection – median age 65.5 [52–78]years. Hospitalization length 4.5 days vs. 9 days (P = 0.0003) and operation time 275 min vs. 142 min (P = 0.004) were statistically different in the robotic vs open group. ICU stay and blood loss were lower in the robotic group, but not statistically significant, age was comparable. Complications according to the Clavien-Dindo classification in the open group: 3× type II, 1× type IIIa, 1× type IIIb, in the robotic group 1× type II and 1× type IIIa. Rehospitalization in the open group was 2×, in the robotic group 1x, always for late postoperative complications. Conclusion: Robotic surgery of the pancreas is currently in its infancy in the Czech Republic. The experience so far with the first ten patients operated on using the DaVinci Xi robotic system has yielded promising results in form of shorter hospitalization, but at cost of longer operating time.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• miniinvazivní chirurgické výkony MeSH
• nemoci slinivky břišní chirurgie   patologie   MeSH
• pankreatektomie * MeSH
• roboticky asistované výkony * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.

• Publikační typ
• časopisecké články MeSH

Úvod a cíl: Primární diagnostika distálních biliárních striktur může být někdy svízelná a obtížná. Je známo, že kartáčková cytologie (BC – brush cytology) má v těchto případech nízkou diagnostickou senzitivitu. Fluorescenční in situ hybridizace (FISH) byla popsána jako užitečná doplňková metoda u pacientů se strikturami žlučových cest. Cílem naší studie bylo stanovit diagnostickou výtěžnost BC, FISH a jejich kombinace (BC + FISH) v primární diagnostice distálních biliárních striktur. Metodika: Tato prospektivní studie byla provedena v období od dubna 2019 do ledna 2021. Do studie byli postupně zařazeni pacienti s dosud nebioptovanými biliárními strikturami, kteří podstoupili první endoskopickou retrográdní cholangiopankreatografii (ERCP) na našem pracovišti. Byly provedeny cytologické a FISH analýzy vzorků tkáně odebraných ze dvou standardizovaných transpapilárních odběrů „kartáčkem“ z distálních striktur. Postoperační histologie nebo výsledky 12měsíčního sledování pacientů byly považovány za zlatý standard pro stanovení konečné diagnózy. Výsledky: Do studie bylo zařazeno celkem 109 pacientů. Sedm pacientů bylo z konečné analýzy vyřazeno a 26 mělo proximální stenózu. Ze zbývajících 76 pacientů (61,8 % mužů, průměrný věk 67,6 let, rozmezí 25–89 let) s distální stenózou byl podíl benigních a maligních striktur 25 (32,9 %), resp. 51 (67,1 %). Z podskupiny maligních striktur tvořilo 17,7 % cholangiokarcinom, 74,5 % nádory pankreatu a 7,8 % jiné nádory. Ve srovnání se samotnou BC zvýšila FISH senzitivitu z 0,373 % na 0,706 % (p = 0,0007) při mírném poklesu specificity (p = 0,045). Závěr: Duální modalita hodnocení tkáně pomocí BC + FISH má lepší senzitivitu pro primární diagnózu distálních biliárních striktur ve srovnání se samotnou BC.

Background and aim: Primary diagnosis of the distal biliary stricture can be sometime difficult. Brush cytology (BC) is known to have low diagnostic sensitivity in these cases. Fluorescence in situ hybridization (FISH) has been reported as a useful adjunctive test in patients with biliary strictures. We aimed to determine performance characteristics of BC, FISH and their combination (BC + FISH) in the primary diagnosis of distal biliary strictures. Methods: This single-center prospective study was conducted between April 2019 and January 2021. Consecutive patients with unsampled biliary strictures undergoing first ERCP in our institution were included. Cytological and FISH analysis of tissue specimens from two standardized transpapillary brushings from the distal strictures were provided. Histopathological confirmation after surgery or 12-month follow-up was regarded as the reference standard for the final diagnosis. Results: A total of 109 patients were enrolled. Seven patients were lost from the final analysis and 26 suffered proximal stenosis. Of the 76 remaining patients (61.8% males, mean age 67.6, range 25–89 years) with distal stenosis, the proportions of benign and malignant strictures were 25 (32.9%) and 51 (67.1%), respectively. Of the subgroup of malignant strictures, 17.7% were cholangiocarcinoma, 74.5% were pancreatic tumors and 7.8% others. In comparison to BC alone, FISH increased the sensitivity from 0.373% to 0.706% (p = 0.0007) with a slight decrease in specificity (p = 0.045). Conclusions: Dual modality tissue evaluation using BC + FISH has better sensitivity for the primary diagnosis of distal biliary strictures, compared to BC alone.

• Klíčová slova
• biliární striktura,
• MeSH
• hybridizace in situ fluorescenční * metody   MeSH
• lidé MeSH
• nemoci žlučových cest * diagnóza   MeSH
• prospektivní studie MeSH
• stenóza diagnóza   MeSH
• žlučové cesty patologie   MeSH
• Check Tag
• lidé MeSH

Úvod: Hepatická tepna se vyznačuje vysokou variabilitou svého průběhu. Cílem této studie je zhodnocení četnosti výskytu jednotlivých typů variantního průběhu v populaci nemocných podstupujících pravostrannou pankreatoduodenektomii (PD), přesnosti předoperačního CT stagingového vyšetření v diagnostice těchto variant a zhodnocení vlivu přítomnosti variantního průběhu hepatické tepny na peroperační a pooperační morbiditu u pacientů podstupujících PD. Metody: Prospektivní observační studie zahrnující 147 pacientů, kteří podstoupili PD pro patologii v oblasti hlavy pankreatu na I. chirurgické klinice Fakultní nemocnice Olomouc v období 1/2015 až 12/2018. Předoperační diagnostika průběhu hepatické tepny byla provedena na základě analýzy stagingového CT vyšetření břicha, výsledek byl klasifikován podle Michelsovy škály a byl korelován s definitivním peroperačním nálezem. Demografická, histopatologická, peroperační a pooperační data pacientů byla součástí prospektivně vedené databáze. Výsledky: Do studie bylo zařazeno celkem 147 pacientů, 83 (56,5 %) mužů a 64 (43,5 %) žen, medián věku 65,0 (37–83) let. Variantní průběh hepatické tepny byl zjištěn u 37 (25,2 %) pacientů. Přesnost předoperační CT diagnostiky v určení typu cévní varianty byla 100 %. Nebyl prokázán statisticky signifikantní rozdíl ve výskytu pooperačních komplikací mezi skupinou pacientů s/a bez variantního průběhu hepatické tepny – CD I–II (50,0 % vs. 47,2 %), CD III–IV (8,3 % vs. 13,8 %). Obdobně je v obou skupinách srovnatelná 30denní (4,2 % vs. 2,4 %) a 90denní mortalita (4,2 % vs. 3,3 %). Závěr: Předoperační diagnostika cévních variant založená na multidetektorovém CT vyšetření břicha je rutinně dostupná a vykazuje vysokou přesnost detekce. Nebyl prokázán rozdíl v pooperační morbiditě a mortalitě u pacientů s a bez přítomnosti variantní hepatické tepny podstupujících PD.

Introduction: Variations in hepatic artery anatomy are very common in the population. The aim of this study is to evaluate the rates of individual types of hepatic artery variants in the population of patients undergoing pancreaticoduodenectomy (PD), assess the accuracy of preoperative staging CT imaging to identify hepatic artery variants, and evaluate the impact of the hepatic artery variants on perioperative and postoperative morbidity of PD patients. Methods: A prospective observation study of 147 patients undergoing PD for a pancreatic head pathology at the 1st Department of Surgery, University Hospital Olomouc between 1/2015–12/2018. Preoperative diagnosis of the course of the hepatic artery was made based on staging CT imaging analysis of the abdomen. The result was classified according to the Michels’ scale and correlated with the final perioperative finding. Demographic, histopathological and clinicopathological data were included in a prospectively maintained database. Results: A total of 147 patients were included in the study, 83 (56.5%) males and 64 (43.5%) females, median age 65.0 (37−83) years. A variant course of the hepatic artery was found in 37 (25.2%) patients. The accuracy of preoperative CT imaging in determining the variant was 100%. The presence of a hepatic artery variant was not statistically significant as a factor in terms of postoperative complications – CD I-II (50.0% vs 47.2%), CD III-IV (8.3% vs 13.8%). Similarly, the 30-day (4.2% vs 2.4%) and 90-day mortality rates (4.2% vs 3.3%) were comparable in both groups. Conclusion: Preoperative diagnosis of vascular variants based on multidetector CT imaging of the abdomen is routinely available and shows high detection accuracy. There was no difference in postoperative morbidity and mortality in patients with and without a variant hepatic artery undergoing PD.

• MeSH
• arteria hepatica * abnormality   anatomie a histologie   diagnostické zobrazování   MeSH
• břicho diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• pankreas chirurgie   patologie   MeSH
• pankreatoduodenektomie * mortalita   škodlivé účinky   MeSH
• počítačová rentgenová tomografie MeSH
• pooperační komplikace epidemiologie   mortalita   MeSH
• pozorovací studie jako téma MeSH
• předoperační vyšetření MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: The painless form of chronic pancreatitis is one of the rarer forms of the disease. While 80% to 90% of all chronic pancreatitis cases have abdominal pain as their clinical symptom, a smaller proportion of persons with chronic pancreatitis do not report typical pain. This form of the disease is often associated with exocrine and endocrine pancreatic insufficiency and weight loss, but the absence of pain symptoms may initially lead to misdiagnosis. METHODS: In a cohort of 257 people with chronic pancreatitis, the painless form was diagnosed in 30 individuals (11.6%), with an average age of 56 years and a predominance of men (71.4%). Thirty-eight percent were non-smokers and 47.6% of patients smoked up to 10 cigarettes per day. Alcohol intake of less than 40 g per day was reported by 61.9% of subjects. A quarter were moderately overweight, with a mean BMI of 26.5. Newly diagnosed diabetes mellitus had 25.7% of the subjects. RESULTS: A frequent finding was the demonstration of morphological changes, with calcifications found in 85,7% and dilatation of the pancreatic duct greater than 6.0 mm in 66%. A surprising finding was the presence of metabolic syndrome in 42.8% and the most frequent finding was the demonstration of decreased external pancreatic secretion (90%). CONCLUSION: Painless chronic pancreatitis is usually treated conservatively. We demonstrate a subset of 28 patients with painless chronic pancreatitis treated surgically. Most frequent indications were benign stenosis of the intrapancreatic bile duct and stenosis of the pancreatic duct. Although approximately 1 in 10 people with chronic pancreatitis present with a painless form of it, so that the form of the disease is described as rare, this does not change the fact that management of these people is still not optimal.

• MeSH
• bolest MeSH
• chronická nemoc MeSH
• chronická pankreatitida * komplikace   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• stenóza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.

• MeSH
• duktální karcinom pankreatu * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nádory slinivky břišní * etiologie   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: Bile duct injury (BDI) remains the most serious complication following cholecystectomy. However, the actual incidence of BDI in the Czech Republic remains unknown. Hence, we aimed to identify the incidence of major BDI requiring operative reconstruction after elective cholecystectomy in our region despite the prevailing modern 4 K Ultra HD laparoscopy and Critical View of Safety (CVS) standards implemented in daily surgical practice among the Czech population. METHODS: In the absence of a specific registry for BDI, we analysed data from The Czech National Patient Register of Reimbursed Healthcare Services, where all procedures are mandatorily recorded. We investigated 76,345 patients who were enrolled for at least a year and underwent elective cholecystectomy during the period from 2018-2021. In this cohort, we examined the incidence of major BDI following the reconstruction of the biliary tract and other complications. RESULTS: A total of 76,345 elective cholecystectomies were performed during the study period, and 186 major BDIs were registered (0.24%). Most elective cholecystectomies were performed laparoscopically (84.7%), with the remaining open (15.3%). The incidence of BDI was higher in the open surgery group (150 BDI/11700 cases/1.28%) than in laparoscopic cholecystectomy (36 BDI/64645 cases/0.06%). Furthermore, the total hospital stays with BDI after reconstruction was 13.6 days. However, the majority of laparoscopic elective cholecystectomies (57,914, 89.6%) were safe and standard procedures with no complications. CONCLUSION: Our study corroborates the findings of previous nationwide studies. Therefore, though laparoscopic cholecystectomy is reliable, the risks of BDI cannot be eliminated.

• MeSH
• cholecystektomie laparoskopická * škodlivé účinky   MeSH
• cholecystektomie škodlivé účinky   MeSH
• iatrogenní nemoci epidemiologie   MeSH
• lidé MeSH
• poranění břicha * chirurgie   MeSH
• registrace MeSH
• žlučové cesty chirurgie   zranění   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH