BACKGROUND/AIMS: The functional lumen imaging probe (FLIP) relies on the principle of impedance planimetry that enables direct measurement of intraluminal pressure, cross-sectional areas, and wall biomechanical properties. The aim of our pilot project was to introduce this method to assess function of the lower oesophageal sphincter and pyloric muscle in experimental pigs. METHODS: All measurements were accomplished in one session in six adult female pigs (mean weight 34.2 ± 3.6 kg), using the EndoFLIP 1.0 System with EndoFLIP catheters. Five major parameters were evaluated: balloon pressure (mm Hg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mm Hg), and zone compliance (mm3/mm Hg). RESULTS: In total, 180 readings were successfully accomplished. Most of the measured values were nearing lower average figures for the lower oesophageal sphincter, and upper average figures for the pylorus in healthy humans. The porcine pyloric sphincter is composed of the Torus pyloricus. It serves as a study "gatekeeper" between the stomach and D1 duodenum, thus explaining higher pyloric readings. There was a clear trend for increasing values of CSA (cross-sectional area), diameter, and balloon pressure with increased filling balloon volumes. However, the sphincter distensibility did not change with increasing filling volumes, either for the lower oesophageal sphincter or pylorus. CONCLUSION: Endoscopic functional luminal planimetry in experimental pigs is feasible, both for the lower oesophageal sphincter and the pylorus. This is an important starting point for future experimental endoscopic trials and pharmacology studies.
- MeSH
- dolní jícnový svěrač * fyziologie diagnostické zobrazování MeSH
- elektrická impedance * MeSH
- pilotní projekty MeSH
- prasata MeSH
- pylorus * MeSH
- tlak MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background/Objectives: Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against N-methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer's disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects. Nevertheless, tacrine is currently facing a renewed wave of interest primarily due to several new tacrine-incorporated hybrids and derivates. There were two specific aims for this study: firstly, to explain the mechanisms of the adverse action of tacrine, as a distinctive example of a highly effective acetylcholinesterase inhibitor; and secondly to check whether luminal impedance planimetry is feasible for preclinical testing of possible side effects of compounds potentially toxic to the gastrointestinal tract. Methods: Six experimental pigs were used as the animal model in this study. Five major parameters were evaluated: luminal pressure (mmHg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mmHg), and zone compliance (mm3/mmHg). All measurements were performed before and 360 min after intragastric administration of 200 mg tacrine (at the porcine tacrine Tmax). Results: This study consistently demonstrated an increase in luminal pressure (a directly measured indicator) for the particular balloon filling volumes used, and inversely a reciprocal decrease in the other parameters after tacrine administration. Conclusions: Endoscopic luminal impedance planimetry is a feasible method to evaluate functional response of the lower oesophageal sphincter to tacrine in experimental pigs. Tacrine did not compromise the function of the lower oesophageal sphincter either toward oesophageal spasms or, in contrast, decreased competence of the lower oesophageal sphincter.
- Publikační typ
- časopisecké články MeSH
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
- 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.
