Pancreas is a vital gland of gastrointestinal system with exocrine and endocrine secretory functions, interweaved into essential metabolic circuitries of the human body. Pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal malignancies, with a 5-year survival rate of 11%. This poor prognosis is primarily attributed to the absence of early symptoms, rapid metastatic dissemination, and the limited efficacy of current therapeutic interventions. Despite recent advancements in understanding the etiopathogenesis and treatment of PDAC, there remains a pressing need for improved individualized models, identification of novel molecular targets, and development of unbiased predictors of disease progression. Here we aim to explore the concept of precision medicine utilizing 3-dimensional, patient-specific cellular models of pancreatic tumors and discuss their potential applications in uncovering novel druggable molecular targets and predicting clinical parameters for individual patients.
- MeSH
- duktální karcinom pankreatu * patologie genetika metabolismus MeSH
- individualizovaná medicína * metody MeSH
- lidé MeSH
- nádory slinivky břišní * patologie genetika MeSH
- techniky 3D buněčné kultury metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- gastrointestinální nádory chirurgie terapie MeSH
- neoadjuvantní terapie MeSH
- Publikační typ
- úvodní články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Along with individual's genetic predisposition, host microbiome is an important factor in etiopathogenesis of gastroesophageal reflux disease (GERD), increasing significantly risk of developing esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). The project aim is to determine markers at the level of microbiome, host genes and their interactions for earlier diagnosis/prediction of BE and EAC The project includes analyses of (1) metagenome and metatranscriptome at several sites of gastrointestinal tract (GIT) in GERD patients, (2) host exome and transcriptome in esophageal tissue in patients with BE/EAC, and (3) genetic profile of GERD patients. Mutations in patient ́s exome/genome and gene expression levels in esophagus tissue will be correlated with microbiome and its functional activity in the GIT and clinical finding with in vivo endomicroscopy. Based on the obtained data, we will propose modification of the standard care regime for GERD patients to avoid progressive/irreversible changes reducing patients ́ life quality or even threating their lives.
Hostitelský mikrobiom spolu s genetickou predispozicí jedince jsou důležitými faktory v etiopatogenezi refluxní choroby jícnu (GERD), která významně zvyšuje riziko rozvoje ezofagitidy (RE), Barrettova jícnu (BE) a adenokarcinomu ezofagu (EAC). Cílem projektu je determinace markerů na úrovni mikrobiomu, genů hostitele a jejich interakcí pro časnější diagnostiku a predikci rozvoje BE a EAC. Projekt obsahuje 3 části: (1) analýzu metagenomu a metatranskriptomu v několika lokalitách gastrointestinálního traktu (GIT) u pacientů s GERD, (2) analýzu hostitelského exomu a transkriptomu ve tkáni jícnu u pacientů s BE/EAC, a (3) analýzu genetického profilu pacientů s GERD a jeho komplikacemi. Mutace v exomu/genomu pacienta a míra exprese genů ve tkáni jícnu budou korelovány s mikrobiomem a jeho funkční aktivitou v GITu a klinickým nálezem doplněným o in vivo endomikroskopii. Na základě získaných dat se pokusíme navrhnout modifikaci standardního režimu péče o pacienty s GERD s cílem předejít pokročilým a ireverzibilním změnám snižujícím kvalitu života pacientů, resp. ohrožujících je na životě.
- Klíčová slova
- sekvenování nové generace, mikrobiom, microbiome, Genetická predispozice, Genetic predisposition, In vivo diagnostika, refluxní choroba jícnu, Barrettův jícen, adenokarcinom jícnu, in vitro diagnostika, Barrett's esophagus, in vitro diagnostics, Next-generation sequencing, Esophageal adenocarcinoma, in vivo diagnostics, metatranskriptom, metatranscriptome, esophageal reflux disease,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Úvod: Cílem práce je retrospektivní analýza pacientů, kteří mezi lety 2010–2023 na Chirurgické klinice LFMU FN Brno podstoupili laparoskopickou resekci karcinomu pankreatu. Metody: Do studie bylo zařazeno 46 pacientů, kteří ve sledovaném období podstoupili laparoskopickou (n=19) nebo otevřenou (n=27) distální pankreatektomii (DP) pro KP. Obě skupiny byly statisticky zhodnoceny a srovnány v následujících parametrech: klinické stadium, grade, počet patologem vyšetřených uzlin, krevní ztráta, délka operace, tříměsíční morbidita a mortalita, doba pobytu na JIP, celková délka hospitalizace, procento readmisí a celkové přežití. Výsledky: Ve skupině otevřené DP bylo více zastoupeno T3 stadium nádoru (81,5 % vs. 57,9 %, p=0,035). Četnější byly v této skupině dediferencované (G3) nádory (18,5 % vs. 5,3 %, p=0,354). Průměrný počet patologem vyšetřených uzlin byl v obou skupinách srovnatelný (otevřená DP 15,1 (min–max, 3−39) vs. lapDP 15,6 (min–max, 5−39). Laparotomický výkon byl spojen s větší průměrnou krevní ztrátou (531 ml vs. 198ml, p=0,002). Byl ale v průměru kratší (190 minut vs. 216 minut, p=0,006). Klinicky závažné komplikace (Dindo III a více), resp. POPF (typ B a C) byly zaznamenány v 10/46 (21,7 %), resp. 14/46 (30,5 %) případech, přičemž nebyl zaznamenán statisticky signifikantní rozdíl mezi oběma skupinami (p=0,489) resp. (p=0,241). Laparoskopický výkon znamenal kratší dobu pobytu na JIP (medián: 5,0 dne vs. 6,0 dne, p=0,396). Celková doba hospitalizace byla u obou skupin shodná (medián: lapDP 12,0 dne vs. otevřená DP 12 dne, p=0,920). Pět pacientů (5/46, 10,9 %) muselo být znovu přijato v průběhu tří měsíců po výkonu. Pravděpodobnost 1,2,3 a pětileté přežití po laparoskopickém, respektive laparotomickém výkonu dosáhlo 76,9 % (95% IS 59,4–99,7 %), 61,5 % (95% IS 41,1−92,2 %), 41,0 % (95% IS 20,5−82,2 %) a 20,5 % (95% IS 6,2−68,2 %), respektive 73,4 % (95% IS 58,3−92,4 %), 33,1 % (95% IS 18,9−57,9 %), 20,7 % (95% IS 9,5−44,9 %) a 20,7 % (95% IS 9,5−44,9 %). Statisticky signifikantní rozdíl v přežití mezi oběma skupinami prokázán nebyl (p=0,484). Závěr: Při srovnání laparoskopické a otevřené DP prováděné pro karcinom pankreatu naše zkušenosti potvrdily, že lapDP je vhodná zejména pro pacienty s menšími nádory lokalizovanými dále od porto-mezenteriální osy. Laparoskopický přístup přinesl nižší krevní ztrátu, zkrácení doby pobytu na jednotce intenzivní péče, srovnatelnou morbiditu a celkové přežití. Relativně dlouhá doba hospitalizace, překvapivě shodná v obou skupinách, nás vedla k zahájení implementace ERAS (enhanced recovery after surgery) protokolu do tohoto segmentu chirurgie.
Introduction: The aim of the study was to perform a retrospective analysis of patients who had undergone laparoscopic resection for pancreatic cancer (PC) at the Department of Surgery of the Faculty of Medicine, Masaryk University and University Hospital Brno, Czech Republic from 2010 to 2023. Methods: Forty-six patients with laparoscopic (n=19) or open (n=27) distal pancreatectomy (DP) for PC were included. Both groups were statistically evaluated and compared in the following parameters: clinical stage, tumor grade, nodes examined by the pathologist, blood loss, duration of surgery, three-month morbidity and mortality, length of ICU stay, overall length of hospital stay, readmission rate and overall survival. Results: There were more T3 tumors in the open DP group (81.5% vs 57.9%, p=0.035). The rate of dedifferentiated (G3) tumors was higher in the open DP group (18.5% vs 5.3%, p=0.354). The mean number of nodes examined by the pathologist was equal in both groups (open DP 15.1 (min– max, 3–39) vs lapDP 15.6 (min–max, 5−39). Laparotomy was associated with a higher mean blood loss (531 ml vs 198 ml, p=0.002). However, it was shorter on average (190 minutes vs 216 minutes, p=0.006). Clinically relevant complications (Dindo III and higher) and POPF (types B and C) were observed in 10/46 (21.7%) and 14/46 (30.5%) cases without any statistically significant difference between both groups (p=0.489 and p=0.241, respectively). The median ICU stay was similar for lapDP and open DP (median: 5.0 days vs 6.0 days, p=0.396). Overall length of hospital stay was identical in both groups (median: lapDP 12.0 days vs open DP 12 days, p=0.920). The three-month readmission rate was 5/46 (10.9%). One-, 2-, 3and 5-year overall survival probability after laparoscopic and open DP was 76.9% (95% CI 59.4−99.7%), 61.5% (95% CI 41,1−92.2%), 41.0% (95% CI 20,5−82.2%) and 20.5% (95% CI 6.2−68.2%), and 73.4% (95% CI 58.3−92.4%), 33.1% (95% CI 18,9−57.9%), 20.7% (95% CI 9.5−44.9%) and 20.7% (95% CI 9.5−44.9%), respectively. No statistically significant difference was observed between both groups (p=0.484). Conclusion: When comparing lapDP and open DP performed for pancreatic cancer, our experience confirmed that lapDP was particularly suitable for patients with smaller tumors located further from the porto-mesenteric axis. The laparoscopic approach was associated with lower blood loss, reduced length of ICU stay, comparable morbidity and overall survival. The relatively long length of hospital stays, surprisingly identical in both groups, prompted us to implement the ERAS (Enhanced Recovery After Surgery) protocol in this surgical field.
- MeSH
- karcinom chirurgie MeSH
- laparoskopie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * chirurgie MeSH
- pankreatektomie MeSH
- pooperační komplikace MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- roboticky asistované výkony * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
INTRODUCTION: The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. METHODS: Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). RESULTS: A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). CONCLUSION: Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.
- Publikační typ
- časopisecké články MeSH
Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications.
BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
- MeSH
- autoimunitní pankreatitida * farmakoterapie diagnóza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- steroidy terapeutické užití aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: The aim of this prospective study was to evaluate the role of serum IL-6 as a potential predictive biomarker of postoperative complications (POC) in elective colorectal surgery. METHOD: A total of 115 patients underwent colorectal surgery for malignancy. IL-6 was measured on the first and third postoperative days (POD1, POD3), and C-reactive protein (CRP) was measured on the POD3. POC was analysed in subgroups according to Clavien‒Dindo (CD), antibiotic (ATB) treatment, intensive care unit (ICU) and hospital length of stay. The predictive power of variables for evaluated endpoints was analysed using receiver-operating characteristic (ROC) analysis and described by area under the curve (AUC). ROC analysis was adopted for the identification of optimal cut-offs. Histological analysis was performed to verify IL-6 production by the tumour. RESULTS: Out of 115 patients who were analysed, 42% had POC. Patients with POC had significantly higher serum levels of IL-6 on POD1 (p < 0.001) and POD3 (p < 0.001). IL-6 early on POD1 as a predictor of antibiotic treatment, ICU stay and hospital stay (AUC 0.818; 0.811; 0.771) did not significantly differ from the AUC of CRP late on POD3 (0.879; 0.838, 0.752). A cut-off IL-6 value of 113 pg/ml on POD1 and 180.5 pg/ml on POD3 in severe complications (CD > 3a) resulted in 75% and 72% sensitivity, 78.6% and 99% specificity, negative predictive value 96.4% and 97% and positive predictive value 29% and 88.9%. CONCLUSION: The serum level of interleukin-6 can predict severe (CD > 3a) POC early on POD1. On POD3, IL-6 is superior to CRP in terms of high positive predictive power of severe POC. Interestingly, the advantage of IL-6 on POD1 is early prediction of the need for antibiotic treatment, ICU stay and hospital stay, which is comparable to the CRP serum level late on the third POD.
