The number of individuals diagnosed with colorectal cancer (CRC) has been on an alarming upward trajectory over the past decade. In some countries, this cancer represents one of the most frequently diagnosed types of neoplasia. Therefore, it is an important demand to study the pathology underlying this disease to gain insights into the mechanism of resistance to treatment. Resistance of tumors to chemotherapy and tumor aggressiveness have been associated with a minor population of neoplastic cells, which are considered to be responsible for tumor recurrence. These types of neoplastic cells are known as cancer stem cells, which have been previously reported to serve an important role in pathogenesis of this malignant disease. Slovakia has one of the highest incidence rates of CRC worldwide. In the present study, the aim was to classify the abundance of selected stem cell markers (CD133, CD166 and Lgr5) in CRC tumors using flow cytometry. In addition, the methylation status of selected genomic regions of CRC biomarkers (ADAMTS16, MGMT, PROM1 (CD133), LGR5 and ALCAM) was investigated by pyrosequencing in a cohort of patients from Martin University Hospital, Martin, Slovakia. Samples from both primary tumors and metastatic tumors were tested. Analysis of DNA methylation in the genomic regions of indicated five CRC biomarkers was also performed, which revealed the highest levels of methylation in the A disintegrin and metalloproteinase with thrombospondin motifs 16 and O6-methyguanine-DNA methyl transferase genes, whereas the lowest levels of methylation were found in genes expressing prominin-1, leucine-rich repeat-containing G-protein-coupled receptor 5 and activated leukocyte cell adhesion molecule. Furthermore, tumor tissues from metastases showed significantly higher levels of CD133+ cells compared with that in primary tumors. Higher levels of CD133+ cells correlated with TNM stage and the invasiveness of CRC into the lymphatic system. Although relatively small number of samples was processed, CD133 marker was consider to be important marker in pathology of CRC.

• Publikační typ
• časopisecké články MeSH

Hepatolithiasis is a benign disease, where stones are localized proximal to the confluence of hepatic ducts. The clinical picture may differ depending on whether the stones cause complete, partial, or intermittent biliary obstruction. The course can vary from asymptomatic to fatal, thus, early diagnosis and treatment is critical for a good prognosis. The gold standard in imaging is magnetic resonance cholangiopancreatography (MRCP). However, correct diagnosis can be challenging due to atypical clinical picture and laboratory findings. We present a case where hepatolithiasis was misdiagnosed initially due to incomplete reporting and documentation of MRCP. Choledocholithiasis was diagnosed based on initial MRCP, and endoscopic stone extraction was indicated. However, an unusual post-interventional course and signs of obstructive cholangitis led to an endoscopic re-intervention, which confirmed absence of pathology in extrahepatic biliary ducts. The cholangitis recurrence required intensive antibiotic treatment, and CT examination revealed intrahepatic S3 bile duct dilatation. Thus, a re-evaluation of initial MRCP and repeated MRCP confirmed hepatolithiasis. Further, laparoscopic bisegmentectomy was chosen as the definitive treatment due to the location of the lesion. The patient recovered and remained symptom free upon a 12 month follow up.

• MeSH
• diferenciální diagnóza MeSH
• hepatektomie MeSH
• laparoskopie MeSH
• lidé MeSH
• litiáza diagnostické zobrazování   chirurgie   MeSH
• magnetická rezonanční cholangiopankreatografie MeSH
• nemoci jater diagnostické zobrazování   chirurgie   MeSH
• počítačová rentgenová tomografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Colorectal cancer (CRC) is one of the leading cancers in both genders. TNM staging system is still the most commonly used tumor classification and prognostic system. The disadvantage of TNM is that the prognostic information it provides is incomplete, and patients with the same histological tumor stages may differ significantly in the clinical outcome. Therefore, the identification of new prognostic parameters is crucial. The carcinogenic process that gives rise to an individual tumor is unique and tumor microenviroment should be taken into consideration. In CRC, T-cell infiltration is not homogenous, and recent studies are mostly focusing on memory T-cells and CD8 cells in predicting disease-free survival (DFS) and overall survival (OS). It seems that DFS and OS are not only dependent on microsatellite instable or stable status but mostly on the levels of expression of the immune signatures. Also, patients with high infiltration of cytotoxic and memory cells have significantly better outcome. This review consolidates current knowledge and recent research about importance of immune-cell-associated proteins, specific gene profiles of immune cells and immunotherapy in CRC. We also discussed cell-specific signatures in cancer treatment.

• MeSH
• imunoterapie MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• kolorektální nádory genetika   imunologie   patologie   MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• prognóza MeSH
• sekvenční analýza RNA MeSH
• staging nádorů MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

One of the most common mechanisms of immune evasion in MSI colorectal cancers (CRCs) is loss of HLA class I expression due to mutations in B2M gene which can become a negative predictor for checkpoint blockade therapy. The aim of this study was the determination of prevalence of B2M somatic mutations in MSI CRC patients and relationship between B2M mutations and lymphocytes infiltration and other clinicopathological features as well as detection of methylation changes in B2M promoter region which can be another mechanism of immune escape. In our study, 37 MSI-H and 5 MSI-L patients were selected for screening of B2M mutational and methylation status. The characterization of patients was based on standard histopathological diagnosis and TNM classification; BRAF, KRAS mutations, tumor-infiltrating lymphocytes and peritumoral lymphoid reaction were also determined. MSI analysis was performed using fragment analysis. B2M mutations were identified by Sanger sequencing, and methylation of CpG islands in promoter region was detected by methylation-specific PCR. Heterozygous mutations in the B2M gene were detected in five MSI-H patients (13.5%), while the mutation c.45_48delTTCT was determined in four patients and mutation c.276delC was found in two patients. One of these five patients was compound heterozygote harboring both mutations. Methylation of the promoter region of the B2M gene was observed in one patient with MSI-H colorectal cancer. Detection of genetic and epigenetic changes in B2M gene could be important in personalized therapy for CRC patients as these changes may be one of the mechanisms of secondary resistance of MSI positive tumors to immunotherapy.

• MeSH
• beta-2-mikroglobulin genetika   MeSH
• CpG ostrůvky MeSH
• dospělí MeSH
• down regulace MeSH
• epigeneze genetická MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• mikrosatelitní nestabilita * MeSH
• mutace MeSH
• promotorové oblasti (genetika) MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů 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

Syndróm Brugadových je genetická porucha charakterizovaná komorovými tachyarytmiami, ktoré môžu viesť k zástave srdca, synkope alebo náhlej srdcovej smrti. Tento syndróm je asociovaný s niekoľkými elektrokardiografickými obrazcami, ako sú napríklad elevácie ST v predných prekordiálnych zvodoch a nekompletná blokáda pravého Tawarovho ramienka. Mnoho ľudí so syndrómom Brugadových nemá žiadne príznaky, ak áno, môžu sa vyskytnúť kedykoľvek a niekedy môžu byť vyvolané horúčkou, alkoholom alebo dehydratáciou. Implantácia implantovateľného srdcového defibrilátora je jediná liečba, ktorá sa osvedčila ako účinná pri liečbe a prevencii náhlej srdcovej smrti u pacientov so syndrómom Brugadových. Uvádzame zriedkavú kazuistiku syndrómu Brugadových, ktorý sa manifestoval komorovou fibriláciou vyvolanou horúčkou.

Brugada syndrome is a genetic disorder characterized by ventricular tachyarrhythmias that may lead to cardiac arrest, syncope or sudden cardiac death. This syndrome is associated with several electrocardiographic patterns such as ST elevations in the anterior precordial leads and incomplete right bundle branch block. Many people with Brugada syndrome do not have any symptoms if yes, they can occur at any time and are sometimes triggered by high temperature, alcohol or dehydration. The implantation of an automatic implantable cardiac defibrillator is the only treatment proven effective in treating and preventing sudden cardiac death in patients with Brugada syndrome. We present a rare case report of Brugada syndrome induced by fever which was manifested with ventricular fibrillation.

• Publikační typ
• abstrakt z konference MeSH