AbstractObjectives MicroRNA-34a (miR-34a) is regulated by \{TP53\} and, in response, downregulates the expression of a gamut of protein-coding genes, including apoptosis regulators, transcription factors, cyclins, and cyclin-dependent kinases. Its upregulation initiates a reprogramming of gene expression and promotes apoptosis. The purpose of this study was the investigation of the potential clinical significance of miR-34a as a molecular prognostic biomarker in colorectal adenocarcinoma using an in-house real-time quantitative \{PCR\} (qPCR) methodology. Design and methods Total \{RNA\} was extracted from 113 primary colorectal adenocarcinoma specimens and 61 paired non-cancerous colorectal tissue samples. After polyadenylation and reverse transcription, miR-34a molecules were determined using qPCR based on \{SYBR\} Green chemistry. Calculations were performed using the comparative \{CT\} method. Finally, extensive biostatistical analysis was performed. Results miR-34a expression does not significantly differ between colorectal adenocarcinoma tissue specimens and adjacent non-cancerous mucosae. However, miR-34a increases progressively as colorectal adenocarcinoma loses its differentiation, being highest in grade İII\} tumors (P = 0.010). Moreover, miR-34a expression is a potential unfavorable prognostic biomarker in colorectal adenocarcinoma, predicting poor disease-free and overall survival (P = 0.002 and P = 0.019, respectively), independently of classical clinicopathological parameters. Most importantly, miR-34a expression stratifies patients without local (N0) and/or distant metastasis (M0) at the time of diagnosis into two groups with substantially different prognosis (P = 0.013 and P = 0.002, respectively). Conclusions High miR-34a levels in colorectal adenocarcinoma predict a rather increased risk for disease recurrence and poor overall survival, particularly in patients at an early \{TNM\} stage. The unfavorable prognostic potential of miR-34a expression is independent of established prognostic features of colorectal adenocarcinoma.

Background: Necrotizing fasciitis (NF) is a group of relatively rare infections, usually caused by two or more pathogens. It affects the skin and subcutaneous tissues of lower and upper limbs, perineal area (Fournier’s gangrene) and the abdominal wall. Early diagnosis and aggressive surgical management are of high significance for the management of this potentially lethal disease. Methods: We conducted a retrospective study in patients who presented,during the last decade,at four University Surgical Departments in the area of Athens, Greece, with an admission diagnosis of NF. Demographic, clinical and laboratory data were gathered, and the preoperative and surgical treatment, as well as the postoperative treatment was analyzed for these patients. Results: A total of 62 patients were included in the study. The mean age of patients was 63.7 (47 male patients). Advanced age (over 65 years) (P<0.01) and female sex (P=0.04) correlated significantly with mortality. Perineum was the mostly infected site (46.8%), followed by the lower limbs (35.5%), and the upper limbs and the axillary region (8.1%). Diabetes mellitus was the most common co-existing disease (40.3%), followed by hypertension (25.8%) and obesity (17,7%). The most common symptom was local pain and tenderness (90.3%). Septic shock occurred in 8 patients (12.9%), and strongly correlated with mortality (P<0.01). Laboratory data were used to calculate retrospectively the LRINEC score of every patient; 26 patients (41.9%) had LRINEC score under 6, 20 patients (32.3%) had LRINEC score 6-8 and 16 patients (25.8%) had LRINEC score >9. Surgical debridement was performed in all patients (mean no. of repeated debridement 4.8), and in 16 cases (25.8%) the infected limb was amputated. The mean length of hospital stay was 19.7 days, and the overall mortality rate of our series was 17.7%. Conclusions: Diagnosis of NF requires high suspect among clinicians, as its clinical image is non-specific. Laboratory tests can depict the severity of the disease; therefore they must be carefully evaluated. Urgent surgical debridement is the mainstay of treatment in all patients; the need of repetitive surgical debridement is undisputed.