BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis, with near-identical incidence and mortality. According to the World Health Organization Globocan Database, the estimated number of new cases worldwide will rise by 70% between 2020 and 2040. There are no effective screening methods available so far, even for high-risk individuals. The prognosis of PDAC, even at its early stages, is still mostly unsatisfactory. Impaired glucose metabolism is present in about 3/4 of PDAC cases. METHODS: Available literature on pancreatic cancer and diabetes mellitus was reviewed using a PubMed database. Data from a national oncology registry (on PDAC) and information from a registry of healthcare providers (on diabetes mellitus and a number of abdominal ultrasound investigations) were obtained. RESULTS: New-onset diabetes mellitus in subjects older than 60 years should be an incentive for a prompt and detailed investigation to exclude PDAC. Type 2 diabetes mellitus, diabetes mellitus associated with chronic non-malignant diseases of the exocrine pancreas, and PDAC-associated type 3c diabetes mellitus are the most frequent types. Proper differentiation of particular types of new-onset diabetes mellitus is a starting point for a population-based program. An algorithm for subsequent steps of the workup was proposed. CONCLUSIONS: The structured, well-differentiated, and elaborately designed approach to the elderly with a new onset of diabetes mellitus could improve the current situation in diagnostics and subsequent poor outcomes of therapy of PDAC.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. AIMS: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. METHODS: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. RESULTS: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5-34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. CONCLUSIONS: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

• MeSH
• dospělí MeSH
• gastrointestinální průchod * MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• pilotní projekty MeSH
• prasata MeSH
• teplota MeSH
• tobolky MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• akademie a ústavy dějiny   MeSH
• gastroenterologie * dějiny   organizace a řízení   MeSH
• nemoci slinivky břišní * MeSH
• Publikační typ
• zprávy MeSH

• O autorovi
• Dítě, Petr, 1941- Autorita

Východiska: Systémová protinádorová imunoterapie představuje zásadní pokrok v současné onkologické léčbě. Avšak tento terapeutický přístup je spojen s riziky nežádoucí gastrointestinální toxicity. Cíl: Tento článek přináší podrobný přehled patogeneze, klinického obrazu, diagnostiky a léčby těchto komplikací. Přehled současného stavu poznání: Inhibitory kontrolních bodů imunitní reakce – imunitních “checkpointů” (check-point inhibitors) zásadně zlepšily prognózu řady maligních onemocnění (mezi které patří např. maligní melanom, nemalobuněčný karcinom plic, rakovina žaludku a kolorektální karcinom osob s patogenními mutacemi, karcinom ledviny, spinocelulární karcinom hlavy a krku a uroteliální karcinom). Patří sem protilátky proti antigenu CTLA-4 (cytotoxický T-lymfocytární antigen 4; především ipilimumab a tremelimumab), dále protilátky proti receptoru programované smrti PD-1 (programmed cell death 1; především pembrolizumab a nivolumab) a proti jeho ligandu PD-L1 (např. atezolizumab a avelumab). V protinádorové imunoterapii se nově začíná využívat také adoptivní buněčná léčba (chimeric antigen receptor T cells – CAR-T cells), a to v léčbě hematologických malignit a metastazujícího kolorektálního karcinomu. Mezi hlavní projevy gastrointestinální toxicity způsobené systémovou protinádorovou imunoterapií patří průjmy (20–50 %), enterokolitida (1–10 %) a laboratorní nebo klinické známky hepatopatie (~10 %). Protinádorová imunoterapie může být komplikována také infekcemi (Clostridium difficile, Mycoplasma a/ nebo cytomegalovirus). I když zatím data o dalších komplikacích chybí, lze předpokládat, že imunoterapie může být komplikována také malabsorpcí žlučových kyselin a syndromem bakteriálního přerůstání v tenkém střevě. Terapie gastrointestinálních komplikací by měla být odstupňována podle tíže postižení. Zahrnuje symptomatickou léčbu (např. loperamid), systémové glukokortikoidy a anti-TNF-alfa monoklonální protilátky (samotné nebo v kombinaci s mykofenolátem mofetilem nebo takrolimem v nejtěžších případech). Závěry: Povědomí o možných komplikacích systémové protinádorové imunoterapie je zásadně důležité pro bezpečnost nemocných. Je třeba pomýšlet na možné imunopatologické nežádoucí vedlejší účinky, komplikující infekce, malabsorpci žlučových kyselin a syndrom bakteriálního přerůstání v tenkém střevě. Promptní náležitá dia gnostika a bezodkladná důrazná léčba zásadně ovlivňují prognózu pacientů. Přísně individualizovaný přístup je nezbytností.

Background: Systemic anti-cancer immunotherapy provides a substantial progress in options of current oncology treatment. Yet, this therapeutic approach is potentially associated with a significant gastrointestinal toxicity. Aim: The purpose of this paper is to provide a comprehensive review on pathogenesis, clinical features, dia gnostics and therapy of these toxicities. Review of current knowledge: Check-point inhibitors brought a major progress in anti-cancer immunotherapy and improved significantly prognosis of several malignancies (e. g. metastatic malignant melanoma, non-small-cell lung cancer, gastric and colorectal cancers in high-risk population associated with presence of pathogenic mutations, renal cell carcinoma, squamous cell carcinoma of the head and neck and urothelial carcinoma). They include monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4; e. g. ipilimumab, tremelimumab), programmed death-1 receptor (PD-1; e. g. pembrolizumab, nivolumab) and its ligand PD-L1 (e. gatezolizumab, avelumab). Chimeric antigen receptor (CAR) T-cell therapy is another new option for haematological malignancies and metastatic colorectal cancer. Major symptoms of gastrointestinal toxicity caused by systemic immunotherapy include diarrhoea (20–50%), entero-colitis (1–10%) and laboratory or clinical signs of hepatopathy (~10%). Anti-cancer immunotherapy can be also complicated by infections (Clostridium difficile, Mycoplasma and/ or cytomegalovirus). There is no data on other possible complications so far. However, it can be assumed that these will also include bile acid malabsorption as well as small intestinal bacterial overgrowth syndrome. Treatment of gastrointestinal complications of immunotherapy should be graded according to their severity. It includes symptomatic medications (e. g. loperamide), systemic glucocorticoids and anti-TNF monoclonal antibodies (alone or together with mycofenolate mofetil or tacrolimus in the most severe cases). Conclusions: Awareness of possible complications of systemic anti-cancer immunotherapy is crucial for patients’ safety. It is mandatory to consider immune-related adverse events, complicating infections, bile acids malabsorption and small intestinal bacterial overgrowth syndrome. Prompt proper dia gnostics and immediate vigorous therapy infl uence the outcome of patients signifi cantly. A strictly individualized approach is indispensable.

• Klíčová slova
• malabsorpce žlučových kyselin, gastrointestinální toxicita, syndrom bakteriálního přerůstání v tenkém střevě,
• MeSH
• imunoterapie * škodlivé účinky   MeSH
• lidé MeSH
• nádory farmakoterapie   MeSH
• nežádoucí účinky léčiv MeSH
• střevní mikroflóra účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Úvod: Téměř všechny preklinické studie u experimentálních prasat je třeba provádět v celkové anestezii. Ketamin je běžně používán jako úvod do anestezie. Avšak dosud nezodpovězenou otázkou je, zda ketamin, antagonista NMDA-receptorů, ovlivňuje motorické funkce žaludku. Cílem této práce bylo vyšetřit žaludeční myoelektrickou aktivitu prasete metodou elektrogastrografie (EGG). Metody: Do studie bylo zařazeno 17 samic Sus scrofa f. domestica (průměrná hmotnost 36,2 ± 3,8 kg). Pro úvod do anestezie byla použita různá léčiva: skupina A (n = 5): medetomidin 0,1 mg/kg i. m.; butorfanol 0,3 mg/kg i. m.; midazolam 0,3 mg/kg i. m.; skupina B (n = 6): azaperon 2,2 mg/kg i. m.; skupina C (n = 6): ketamin 20 mg/kg i. m.; azaperon 2,2 mg/kg i. m. Celková anestezie ve všech skupinách pokračovala podáváním 1% propofolu (opakované 1ml bolusy, celkem 10–12 ml i.v.). Záznam EGG začal za 15 min. po úvodu do anestezie a trval 30 min. Výsledky byly vyhodnoceny jako dominantní frekvence pomalých žaludečních vln (DF) a plochy pod křivkou (EGG power). Výsledky: Celkem bylo vyhodnoceno 510 jednominutových EGG intervalů (každý dvakrát: DF a power). DF byly (průměr ± směrodatná odchylka): 1,4 ± 0,4 (skupina A), 1,3 ± 0,3 (skupina B) a 0,2 ± 0,1 cykly/min. (skupina C). Rozdíly mezi skupinou C a skupinami A a B byly statisticky významné (p < 0,001). Mediány ploch pod křivkou (IQR) byly: 0,13 (0,02–0,44; skupina A); 0,13 (0,03–0,54; skupina B) a 0,30 V2 (0,07–1,44; skupina C). Rozdíl mezi skupinami A a C byl na hranici statistické významnosti (p = 0,066; chyba 2. typu beta 0,295). Závěry: Ketamin, a to i v jedné intramuskulární dávce, ovlivňuje myoelektrické funkce žaludku prasete. Proto by neměl být používán v preklinických studiích gastrointestinální motility experimentálních prasat.

Introduction: Preclinical studies in experimental pigs are carried out mostly under general anaesthesia. Ketamine is commonly used for induction of anaesthesia. However, there are concerns that ketamine, an NMDA-receptor antagonist, may influence gastric motor function. The aim of this study was to investigate porcine gastric myoelectric activity by means of electrogastrography (EGG). Methods: Seventeen female animals (mean weight 36.2±3.8 kg) were enrolled. Drugs used for induction of anaesthesia were: Group A (n=5): medetomidine 0.1 mg/kg i. m.; butorphanol 0.3 mg/kg i. m.; midazolam 0.3 mg/kg i. m.; Group B (n=6): azaperon 2.2 mg/kg i. m.; Group C (n=6): ketamine 20 mg/kg i. m.; azaperon 2.2 mg/kg i. m., followed in all groups by i.v. 1% propofol (repeated one-mL boluses, 10–12 mL in total). EGG recording started 15 min. after the induction administration and lasted 30 min. Results were evaluated as the dominant frequency of gastric slow waves (DF) and EGG power (areas of amplitudes). Results: In total, 510 one-minute EGG intervals were assessed. DFs were (mean ± standard deviation): 1.4±0.4 (Group A), 1.3±0.3 (Group B) and 0.2±0.1 cycles per min. (Group C). The differences between group C and groups A and B were statistically significant (p<0.001). Median power (IQR) was 0.13 (0.02–0.44; Group A), 0.13 (0.03–0.54; Group B) and 0.30 V2 (0.07–1.44; Group C). The difference between groups A and C was of borderline significance (p=0.066; type 2 error beta 0.295). Conclusions: Ketamine, administered even in a single intramuscular dose, affected myoelectric function of the porcine stomach. Therefore, it should be avoided in gastrointestinal motility studies in experimental pigs.

• MeSH
• elektromyografie metody   MeSH
• gastrointestinální motilita * účinky léků   MeSH
• ketamin * MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• receptory N-methyl-D-aspartátu * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• Helicobacter pylori patogenita   MeSH
• infekce vyvolané Helicobacter pylori * komplikace   patofyziologie   MeSH
• karcinogeny MeSH
• lidé MeSH
• nádory žaludku epidemiologie   etiologie   patofyziologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.

• MeSH
• dextrany MeSH
• idiopatické střevní záněty chemicky indukované   terapie   MeSH
• Lactobacillus casei * MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• probiotika farmakologie   MeSH
• sírany MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Galantamine has been used as a treatment for Alzheimer disease. It has a unique, dual mode of action (inhibitor of acetylcholinesterase and allosteric modulator of nicotinic acetylcholine receptors). Nausea (in about 20%), vomiting (10%) and diarrhoea (5-7%) are the most common side effects. The aim of this study was to assess the effect of galantamine on porcine gastric myoelectric activity without (Group A) and with (Group B) dextran sodium sulphate (DSS)-induced gastrointestinal injury. Galantamine hydrobromide was administrated to twelve pigs as a single intragastric dose (24 mg). Gastric myoelectric activity was investigated by electrogastrography (EGG). Basal (15 min before galantamine administration) and study recordings after galantamine administration (300 min) were evaluated using a running spectral analysis. Results were expressed as dominant frequency of gastric slow waves and power analysis (areas of amplitudes). Altogether, 3780 one-minute EGG recordings were evaluated. In Group A, power was steady from basal values for 180 min, then gradually decreased till 270 min (p = 0.007). In Group B, there was a rapid gradual fall from basal values to those after 120 min (p = 0.007) till 300 min (p ˂ 0.001). In conclusion, galantamine alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of galantamine-associated dyspepsia in humans. DSS caused further profound decrease of EGG power. That may indicate that underlying inflammatory, ischaemic or NSAIDs-induced condition of the intestine in humans can have aggravated the effect of galantamine on gastric myoelectric activity.

• Publikační typ
• časopisecké články MeSH

Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.

• MeSH
• donepezil chemie   farmakokinetika   farmakologie   MeSH
• gastrointestinální trakt účinky léků   patologie   patofyziologie   MeSH
• indany metabolismus   MeSH
• kapslová endoskopie MeSH
• metabolom * účinky léků   MeSH
• migrující myoelektrický komplex * účinky léků   MeSH
• piperidiny metabolismus   MeSH
• prasata MeSH
• síran dextranu MeSH
• žaludek účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH