PURPOSE: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective. METHODS: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 μg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12. RESULTS: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%). CONCLUSION: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease.
- MeSH
- Crohnova nemoc * farmakoterapie imunologie MeSH
- dospělí MeSH
- feces chemie MeSH
- infliximab * terapeutické užití imunologie aplikace a dávkování MeSH
- injekce subkutánní MeSH
- intravenózní podání MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- terapie neúspěšná MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Experimental evidence has revealed that phosphodiesterase five inhibitors (PDE5is) increase epithelial barrier function and suppress intestinal carcinogenesis. Few epidemiological studies have investigated the role of PDE5i in increasing the risk of colorectal cancer (CRC); however, these studies have proffered varying conclusions. We therefore aimed to perform a comprehensive review and meta-analysis to investigate whether PDE5i use is associated with the incidence of CRC. METHODS: Databases, namely, PubMed, Scopus, Embase, and Web of Science, were used for literature search. Observational studies (published until January 31, 2021) that assessed the association of PDE5i use with CRC incidence were considered. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model. RESULTS: We identified four retrospective studies that involved 965,044 participants and 3,518 CRC cases detected during a mean follow-up of 12.7 years. Pooled results indicated a significantly reduced CRC risk among all PDE5i users (RR, 0.85; 95% CI, 0.76-0.95; P = 0.004, I2 = 63%). Moreover, continuous use of PDE5i was associated with a significantly reduced risk of CRC (RR, 0.63; 95% CI, 0.59-0.68; P < 0.001, I2 = 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98-1.02; I2 = 84.7%). CONCLUSION: Our findings suggest that continuous use of PDE5i was associated with a significantly reduced risk of CRC development. Future studies with a longitudinal design and adequate control of confounding factors are required to clarify whether a longer duration of PDE5i use alters the risk of CRC.
PURPOSE: Crohn's disease (CD) belongs to chronic disorders with unpredictable disease course. The aim of this study was to identify how genetic testing (NOD2/CARD15) can be used in patients with CD to predict the need for surgical treatment (to define an aggressive type of disease where the patient can profit from early surgery). METHODS: The patients who were tested genetically had undergone a surgery due to CD at the Department of Surgery University Hospital Brno Bohunice between 2010 and 2016. The control group consisted of patients with CD who had been diagnosed with CD at least 5 years prior to the testing and had not required any surgical intervention. The second control group was healthy subjects. RESULTS: In total, there were 117 operated patients for CD, 77 patients with CD that had not undergone surgery for CD and 30 healthy subjects. For patients with at least one genetic mutation, the risk of the necessity of surgical treatment of CD is 1.96 times higher than for patients with no mutation. Patients with two or more mutations were generally operated on at a younger age, in a shorter time after being diagnosed and each patient had a partial resection of the ileum. CONCLUSION: The group of operated patients with CD had a significantly higher distribution of at least one genetic mutation as opposed to the non-operated group. In patients with two or more mutations, the disease course was more aggressive. This group of patients might profit from the conservative top-down or early surgical therapy.
- MeSH
- alely MeSH
- Crohnova nemoc genetika chirurgie MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace genetika MeSH
- prognóza MeSH
- rizikové faktory MeSH
- signální adaptorový protein Nod2 genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIM: Foreshortened mesentery or thick abdominal wall constitutes a rationale for laparoscopic intracorporeal ileocolic anastomoses (ICA). The aim of this study was to compare intracorporeal to extracorporeal ICA in terms of surgical site infections in patients with Crohn's ileitis and overweight patients with right colon tumors. METHOD: This was a prospective propensity score-matched cohort study enrolling consecutive patients with Crohn's terminal ileitis and overweight patients with right colon tumors undergoing elective laparoscopic right colon resection with intracorporeal or extracorporeal ICA. Propensity score matching with a 1:1 ratio was employed to compare diagnosis-matched patients for age, BMI, ASA, and previous abdominal surgery. RESULTS: Overall, 453 patients were enrolled: 233 intracorporeal vs. 220 extracorporeal. Propensity score matching left 195 intracorporeal and 195 extracorporeal patients comparable for age (p = 0.294), gender (p = 0.683), ASA (p = 0.545), BMI (p = 0.079), previous abdominal surgery (p = 0.348), and diagnosis (p = 0.301). Conversion rates (5.1 vs. 3.6%; p = 0.457) and intraoperative complications (1 vs. 2.1%; p = 0.45) were similar. Overall morbidity (5.1 vs. 12.8%; p = 0.008) and re-intervention rates (3.1 vs. 8.7%; p = 0.029) were significantly higher in extracorporeal patients. Anastomotic leak rates (0.5 vs. 1.5%; p = 0.623) did not differ. Incisional SSI rate was significantly higher in extracorporeal patients (p = 0.01). CONCLUSION: Laparoscopic intracorporeal ICA reduced incisional SSI rates as compared to its extracorporeal counterpart.
- MeSH
- anastomóza chirurgická škodlivé účinky MeSH
- ileum chirurgie MeSH
- infekce chirurgické rány epidemiologie prevence a kontrola MeSH
- kohortové studie MeSH
- kolon chirurgie MeSH
- laparoskopie * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- perioperační péče MeSH
- pooperační komplikace etiologie MeSH
- tendenční skóre * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
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.
- MeSH
- citráty aplikace a dávkování škodlivé účinky MeSH
- kolonoskopie * MeSH
- kyselina askorbová aplikace a dávkování škodlivé účinky MeSH
- kyselina citronová aplikace a dávkování škodlivé účinky MeSH
- léčebná irigace škodlivé účinky metody MeSH
- lidé MeSH
- organokovové sloučeniny aplikace a dávkování škodlivé účinky MeSH
- pikoliny aplikace a dávkování škodlivé účinky MeSH
- polyethylenglykoly aplikace a dávkování škodlivé účinky MeSH
- projímadla aplikace a dávkování škodlivé účinky MeSH
- prospektivní studie MeSH
- purgativa aplikace a dávkování škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- akutní bolest břicha komplikace MeSH
- Crohnova nemoc komplikace MeSH
- dospělí MeSH
- komplikace těhotenství patologie MeSH
- lidé MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
PURPOSE: MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC. METHODS: We examined the expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon cancer cells and examined the effects of miR-21 silencing on viability, apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells. RESULTS: The expression levels of miR-21 were significantly increased in CRC tumor tissue (P < 0.0001). Significant differences in miR-21 levels were observed also between CRC tissues of patients with CRC in different clinical stages: I vs. II (P = 0.033) and I vs. IV (P = 0.021). Kaplan-Meier analysis proved that the miR-21 expression levels are correlated to shorter overall survival of CRC patients (P = 0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability; however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it contributed to the decrease of cell viability. Suppression of miR-21 decreased cell migration ability of DLD-1 cells by nearly 30 % (P = 0.016). CONCLUSION: We have confirmed the overexpression of miR-21 in CRC samples and its correlation with advanced disease and shorter overall survival. These findings could be described in part by the fact that CRC cells with increased expression of miR-21 have higher migration ability.
- MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- apoptóza účinky léků genetika MeSH
- buněčný cyklus účinky léků genetika MeSH
- Kaplanův-Meierův odhad MeSH
- kolorektální nádory farmakoterapie genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA antagonisté a inhibitory genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory tračníku genetika patologie MeSH
- pohyb buněk účinky léků genetika MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- viabilita buněk účinky léků genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: The aim of this study was to determine whether overactivity of the anal sphincter in patients with hemorhhoids is primary or secondary and thus assess indication of lateral internal sphincterotomy to surgical treatment of hemorrhoids. Tonic contraction of the sphincter muscle in patients with advanced stages of hemorrhoids is considered by many authors as a primary cause, and therefore, they complete hemorrhoid surgery with lateral internal sphincteroomy. If hypertension of anal sphincter is secondary during hemorrhoid disease, lateral internal sphincterotomy is not indicated. Although examinations made immediately after sphincterotomy proved no changes of anal continence, certain sequelae of lateral internal sphincterotomy cannot be excluded and may later negatively affect patient's anal continence. PATIENTS AND METHODS: The prospective study comprised 385 patients treated in 2002-2006 by Hemoron or surgery according to Milligan-Morgan or Longo. Patients with history of another disease of the anal canal, radiotherapy of pelvis, Crohn's disease or ulcerous colitis were excluded. Manometry was performed before and after surgery at intervals of 1, 3, 6 and 12 months after operation using a perfusion flow method, six-channels catheter with radial arrangement of channel tips. RESULTS: In all three groups (Hemoron, sec. Milligan-Morgan, sec. Longo), there were 60-65% of patients with third degree hemorrhoids. Normal resting anal pressure before surgery was recorded in only 25% of men and 30% of women. Patients with advanced hemorrhoid degrees were found to have significant hypertension of the anal sphincter. The most significantly improved state of sphincter overactivity was observed after surgery according to Longo and application of Hemoron. After surgery, according to Milligan-Morgan, recovery of anal sphincter tension was the longest; even 6 months after operation, a mean increased resting anal pressure persisted (91-110 mmHg) in 25% of men and 19% of women. After 12 months, recovery of anal tension occurred in this group also--mean increased anal pressure was recorded in only three patients (1.67%). CONCLUSION: Overactivity of the anal sphincter in patients with hemorrhoids is secondary and according to our results. Hypertension of the sphincter muscle in patients with hemorrhoids is significantly increased in patients with advanced degrees of hemorrhoids. Therefore, it is not recommended to postpone surgery and indicate patients with advanced degrees of hemorrhoids to hemorrhoidectomy.
- MeSH
- anální kanál patofyziologie chirurgie MeSH
- časové faktory MeSH
- chirurgie trávicího traktu škodlivé účinky MeSH
- fekální inkontinence etiologie patofyziologie MeSH
- hemoroidy komplikace patofyziologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- manometrie MeSH
- obnova funkce MeSH
- prospektivní studie MeSH
- rektum patofyziologie MeSH
- stupeň závažnosti nemoci MeSH
- svalová kontrakce MeSH
- tlak MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
BACKGROUND: Genetic variability in obesity-related genes and the resulting phenotypes are being recognized as major risk factors for colorectal cancer and/or severity of the disease.
- MeSH
- angiotensinogen genetika MeSH
- běloši genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kolorektální nádory genetika komplikace MeSH
- leptin genetika MeSH
- leptinové receptory genetika MeSH
- lidé MeSH
- obezita genetika komplikace MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- adenokarcinom etiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory anu etiologie MeSH
- nádory rekta chirurgie komplikace MeSH
- proktokolektomie rekonstrukční MeSH
- střevní sliznice chirurgie MeSH
- ulcerózní kolitida chirurgie komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
