Tomáš Grolich

Serum-based microRNA signatures in early diagnosis and prognosis prediction of colon cancer

Early detection of colorectal cancer is the main prerequisite for successful treatment and reduction of mortality. Circulating microRNAs were previously identified as promising diagnostic, prognostic and predictive biomarkers. The purpose of this study was to identify serum microRNAs enabling early diagnosis and prognosis prediction of colon cancer. In total, serum samples from 427 colon cancer patients and 276 healthy donors were included in three-phase biomarker study. Large-scale microRNA expression profiling was performed using Illumina small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs was validated on independent training and validation sets of samples using RT-qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four-microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c-3p was established (AUC = 0.917), distinguishing colon cancer patients from healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This panel of microRNAs exhibited high diagnostic performance also when analyzed separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC = 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66; P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs enabling non-invasive early detection and prognosis prediction of colon cancer were identified.

Self-expandable biodegradable biliary stents in porcine model

BACKGROUND Treatment or prevention of a benign biliary tree stricture is an unresolved problem. A novel self-expandable biodegradable polydioxanon biliary stent in a porcine model was studied. MATERIALS AND METHODS This new stent was used in 23 pigs. Feasibility and safety of surgical stenting, time of biodegradation, and histologic reaction in 2, 8, 13, and 20 wk of a follow-up were studied. All stents were inserted into a common bile duct through a duodenal papilla following small dilatation. After surgical evaluation of abdominal cavities, the pigs were sacrificed to remove common bile ducts with the stents. All bile ducts were assessed by macroscopic and histopathologic examination. RESULTS Self-expansion was correct in all cases. Neither bile duct obstruction nor postsurgical complications were observed. Macroscopic evaluation indicated lightening of the stent color in 2 wk, a partial disintegration in 8 wk, and a complete absorption in 13 and 20 wk. Histologic evaluation in general substantiated a mild-to-moderate inflammatory reaction in the lamina propria during the whole follow up and had no clinical consequences. No cholangitis, necrosis, abscess, or excessive fibroplasia was found in a hepatoduodenal ligament. CONCLUSIONS Our results suggest that polydioxanon biodegradable self-expanding stents seem to be useful for biliary system implantation, offer a good biocompatibility, and completely degrade within 13 wk.

Comparison of cervical anastomotic leak and stenosis after oesophagectomy for carcinoma according to the interval of the stomach ischaemic conditioning

BACKGROUND Stomach preparation by ischaemic conditioning prior to oesophageal resection represents a potential method of reducing the risk of anastomotic complications. This study compares the results of the anastomotic complications of cervical anastomosis after oesophagectomy with a short interval after ischaemic conditioning (group S) and a long interval (group L). METHODS Subjects undergoing oesophagectomy for carcinoma after ischaemic conditioning were divided into two groups. Group S had a median interval between ischaemic conditioning and resection of 20 days, while for group L the median interval was 49 days. Anastomotic leak and anastomotic stenosis in relation to the interval between ischaemic conditioning and actual resection were followed. RESULTS After ischaemic conditioning, 33 subjects in total underwent surgery for carcinoma; 19 subjects in group S and 14 subjects in group L. Anastomotic leak incidence was comparable in both groups. Anastomotic stenosis occurred in 21% of cases in group S and 7% of cases in group L (not statistically significant). CONCLUSIONS A long interval between ischaemic conditioning and oesophagectomy does not adversely affect the postoperative complications. A lower incidence of anastomosis stenoses was found in subjects with a longer interval, however, given the size of our sample, the statistical significance was not demonstrated. Both groups seem comparable in surgical procedure course and postoperative complications.