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A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.

MeSH
adenom genetika patologie MeSH
karcinom in situ genetika patologie MeSH
kolorektální nádory genetika patologie MeSH
lidé MeSH
metylace DNA MeSH
mikrosatelitní nestabilita * MeSH
mutace * MeSH
nádorové biomarkery genetika MeSH
následné studie MeSH
prognóza MeSH
senioři MeSH
Check Tag
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

A head-to-head comparison of 4-L polyethylene glycol and low-volume solutions before colonoscopy: which is the best? A multicentre, randomized trial

International journal of colorectal disease. 2017 ; 32 (12) : 1763-1766. [pub] 20170924

Int J Colorectal Dis
ISSN 1432-1262
Medvik
Zdroj

PURPOSE: The purpose of this study is to compare the efficacy and tolerability of polyethylene glycol (PEG) to sodium picosulfate/magnesium citrate (SPMC) and low-volume polyethylene glycol/ascorbic acid (PEGA) in a single- or split-dose regimen for colonoscopy bowel preparation. METHODS: This was a prospective, randomized, endoscopist-blinded, multicentre study. Outpatients received either PEG or SPMC or PEGA in a single or a split dose before the colonoscopy. Quality and tolerability of the preparation and complaints during preparation were recorded. RESULTS: Nine hundred seventy-three patients were analysed. Satisfactory bowel cleansing (Aronchick score 1 + 2) was more frequent when a split dose was used irrespective of the solution type (PEG 90.1 vs 68.8%, PEGA 86.0 vs 71.6%, SPMC 84.3 vs 60.2%, p < 0.001). SPMC was the best tolerated followed by PEGA (p < 0.006) and PEG as the worst (p < 0.001). Tolerability did not correlate with the regimen and amount of the solution used. Female gender is associated with a higher incidence of nausea, vomiting and pain (p < 0.029). CONCLUSIONS: Both PEG, PEGA and SPMC are fully comparable in terms of colonic cleansing when used in similar regimens. The split-dose preparation is more effective in all agents. SPMC and PEGA are better tolerated than PEG. The preparation regimen and/or the volume do not affect tolerability.

Abstrakt

Case report - psoriáza jako paradoxní nežádoucí účinek anti TNF-α terapie IBD

Gastroenterologie a hepatologie. 2017 ; 71 (S2) : 2S49.

Gastroenterol. hepatol. (Print)
ISSN 1804-7874
Medvik
Zdroj

6. kongres České gastroenterologické společnosti. 2017 ; () : 2S49.

Medvik
Zdroj

Publikační typ
abstrakt z konference MeSH

Článek

Inflammation regulates 11β-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system

Steroids. 2017 ; 126 (-) : 66-73. [pub] 20170725

ISSN 1878-5867
Medvik
Zdroj

The bioavailability of glucocorticoids is modulated by enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), which catalyzes the conversion of inactive 11-oxo-glucocorticoids to active 11-hydroxy-glucocorticoids cortisol and corticosterone and is regulated by pro-inflammatory cytokines. Our aim was to assess the effect of colitis on the expression of 11HSD1 in specific microanatomical compartments of the mucosal immune system. Using qRT-PCR we quantified the expression of 11HSD1 and cytokines in the colon, mesenteric lymph nodes (MLN) and spleen of mice with colitis. Microsamples of the MLN cortex, paracortex and medulla, colonic crypt epithelium (CCE), lamina propria and isolated intestinal lymphoid follicles (ILF) were harvested by laser microdissection, whereas splenic and MLN lymphocytes by flow cytometry. Colitis increased 11HSD1 in the CCE, ILF, and MLN cortex but not in the lamina propria and the MLN paracortex and medulla. Expression of IL-4, IL-21 and TNFα was increased in both the cortex of MLN and ILF, whereas IL-1β and IL-10 were only increased in the follicles. No positive effect was observed in the case of IFNγ and TGFβ. 11HSD1 was positively correlated with TNFα and less strongly with IL-21, IL-1β, and IL-4. Colitis also upregulated the 11HSD1 expression of T cells in the spleen and MLN. The study demonstrates the stimulatory effect of inflammation on local glucocorticoid metabolism only in particular compartments of the mucosal immune system. The correlation between cytokines and 11HSD1 in the ILF and MLN cortex indicates that pro-inflammatory cytokines may amplify glucocorticoid signals in inductive compartments of the mucosal immune system.

MeSH
11-beta-hydroxysteroiddehydrogenasa typ 1 genetika metabolismus MeSH
cytokiny metabolismus MeSH
kolitida enzymologie genetika imunologie MeSH
myši inbrední BALB C MeSH
myši MeSH
regulace genové exprese enzymů MeSH
střevní sliznice imunologie MeSH
zánět enzymologie genetika imunologie MeSH
zvířata MeSH
Check Tag
mužské pohlaví MeSH
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Efektivní příprava střeva před koloskopií – nízkoobjemový PEG v děleném režimu
[Effective bowel preparation before coloscopy – low-volume PEG in the divided dose regimen]

Vnitřní lékařství. 2016 ; 62 (4) : 249-254.

ISSN 0042-773X
Medvik
Zdroj

Úvod: Kvalitní vyčištění střeva je pro úspěch koloskopie klíčové. Standardní přípravou jsou 4 l polyetylenglykolu (PEG). Nově je k dispozici kombinace PEG a kyseliny askorbové (PEGA) o polovičním objemu. Kromě typu přípravku hrají roli při přípravě střeva i časové faktory, které nejsou vyjasněné. Cílem práce bylo porovnat účinnost a toleranci obou přípravků a zhodnotit vliv časového režimu přípravy. Metody: Do hodnocení bylo zařazeno celkem 380 osob ve 4 skupinách, které použily 4 l PEG (Fortrans) v jedné dávce nebo rozděleně 3 + 1 l a PEG + kyselina askorbová (Moviprep) rozděleně 1 + 1 l nebo 2 l den před vyšetřením. Výsledky: Mezi přípravky nebylo rozdílu v kvalitě přípravy střeva, pokud byly použity ve stejném režimu. Vyčištění střeva bylo v obou případech lepší při dělené přípravě (p < 0,001) a nepřímo úměrně korelovalo s délkou přípravy (p = 0,003) a přímo úměrně s dobou od konce přípravy do koloskopie (p < 0,001). PEGA byl lépe tolerován (p < 0,028), bez ohledu na režim přípravy. Závěr: PEG a PEGA jsou obdobně účinné v přípravě střeva před koloskopií za předpokladu, že jsou použity v podobném režimu. Nejlepší výsledky má rozdělení přípravy do 2 dnů. PEGA je lépe tolerován než PEG, bez ohledu na použitý režim. Kvalitu vyčištění střeva ovlivňuje délka vlastní přípravy (nejlépe do 12 hod) a doba od přípravy do vyšetření (do 8 hod).

Introduction: The good and safe bowel cleansing is key to the success of coloscopy. The standard preparation involves 4 l polyethylene glycol (PEG). Now the combination of PEG and ascorbic acid (PEGA) of half the volume is available. Besides the type of product also the time factors which are not clarified, play a role during the bowel preparation. The aim of the study was to compare the efficiency and tolerance of both the agents and evaluate the effect of the time regimen of preparation. Methods: 380 individuals were included in the evaluation in 4 cohorts which used 4 l PEG (Fortrans) in a single dose or split into 3 + 1 l and PEG + ascorbic acid (Moviprep) split into 1 + 1 l or 2 l one day before examination. Results: There was no difference between the agents as to the quality of bowel preparation, when they were used in the same regimen. The bowel cleansing was better in both cases in the divided dose regimen (p < 0.001), and it was inversely proportional to the length of preparation (p = 0.003) and directly proportional to the length of time between the end of preparation and coloscopy (p < 0.001). PEGA was better tolerated (p < 0.028), regardless of the preparation regimen. Conclusion: PEG and PEGA are similarly efficient in the bowel preparation before coloscopy provided they are used in a similar regimen. The best results are reached when the preparation is divided into 2 days. PEGA is better tolerated than PEG, regardless of the used regimen. The quality of bowel cleansing is affected by the length of preparation (optimally up to 12 hours) and the time elapsed from the preparation until examination (up to 8 hours).