Identifying the main barriers for participation in a population-based colorectal cancer screening programme in East Azerbaijan, Iran.

Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. However, CRC is considered as one of the most preventable cancers by which the mortality rates reduce about 60% through implementing the screening programmes. The present study aimed to evaluate the main barriers of CRC screening in a defined population. Method: Healthy individuals from all regions of the state were invited to participate in different healthcare centres. They were assessed by a provided online risk assessment tool, which was completed for all recruited subjects, and has been developed to assess the CRC risk based on personal and family history of adenoma, CRC, and other high-risk diseases. Research team staff assessed all individuals by this tool and then eligible people according to their lifetime risk of CRC were included in the study. There was not any age restriction in this study. Colonoscopy and three stool-based tests including faecal occult blood test, faecal immunochemical test and stool DNA tests were performed. Results: Overall, 725 cases including 425 (58.6%) males and 300 (41.4%) females participated in the study. Lack of knowledge and attitude about screening programmes was the most common barrier, especially among women (68% for women versus 58% for men) and those from rural areas (88% in rural versus 55% in urban areas). Fear of colonoscopy and procedure complications and pain (48%), discomfort and anxiety from inserting a tube into the bowel (65% among females versus 43% among males) were reported commonly. Embarrassment and dignity were other complaints, especially in women (62% in females versus 35% in males). Conclusion: Increasing knowledge and attitude about the aims and benefits of screening programmes, acceptable and convenient communication of health systems with the general population are considered to be the key elements in the success and implementation of any screening programme.

Escherichia coli and Colorectal Cancer: Unfolding the Enigmatic Relationship.

Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways. Mucosa-associated E. coli strains are more prevalent in CRC biopsies in comparison to healthy controls. Moreover, these strains can survive and replicate within macrophages and induce a pro-inflammatory response. Chronic exposure to inflammatory mediators can lead to increased cell proliferation and cancer. Production of colobactin toxin by the majority of mucosa-associated E. coli isolated from CRC patients is another notable finding. Colibactin-producing E. coli strains, in particular, induce double-strand DNA breaks, stop the cell cycle, involve in chromosomal rearrangements of mammalian cells and are implicated in carcinogenic effects in animal models. Moreover, some enteropathogenic E. coli (EPEC) strains are able to survive and replicate in colon cells as chronic intracellular pathogens and may promote susceptibility to CRC by downregulation of DNA Mismatch Repair (MMR) proteins. In this review, we discuss current evidence and focus on the mechanisms by which E. coli can influence the development of CRC.

Mucosa-Associated Escherichia coli in Colorectal Cancer Patients and Control Subjects: Variations in the Prevalence and Attributing Features.

Accumulating evidence indicates that specific strains of mucosa-associated Escherichia coli (E. coli) can influence the development of colorectal carcinoma. This study aimed to investigate the prevalence and characterization of mucosa-associated E. coli obtained from the colorectal cancer (CRC) patients and control group. At two referral university-affiliated hospitals in northwest Iran, 100 patients, 50 with CRC and 50 without, were studied over the course of a year. Fresh biopsy specimens were used to identify mucosa-associated E. coli isolates after dithiothreitol mucolysis. To classify the E. coli strains, ten colonies per sample were typed using enterobacterial repetitive intergenic consensus-based PCR (ERIC-PCR). The strains were classified into phylogroups using the quadruplex PCR method. The PCR method was used to examine for the presence of cyclomodulin, bfp, stx1, stx2, and eae-encoding genes. The strains were tested for biofilm formation using the microtiter plate assay. CRC patients had more mucosa-associated E. coli than the control group (p < 0.05). Enteropathogenic Escherichia coli (EPEC) was also found in 23% of CRC strains and 7.1% of control strains (p < 0.05). Phylogroup A was predominant in control group specimens, while E. coli isolates from CRC patients belonged most frequently to phylogroups D and B2. Furthermore, the frequency of cyclomodulin-encoding genes in the CRC patients was significantly higher than the control group. Around 36.9% of E. coli strains from CRC samples were able to form biofilms, compared to 16.6% E. coli strains from the control group (p < 0.05). Noticeably, cyclomodulin-positive strains were more likely to form biofilm in comparison to cyclomodulin-negative strains (p < 0.05). In conclusion, mucosa-associated E. coli especially cyclomodulin-positive isolates from B2 and D phylogroups possessing biofilm-producing capacity colonize the gut mucosa of CRC patients.

Efficacy of Sovodak in the Management of Patients Co-infected with HIV/HCV.

Purpose: Sofosbuvir (SOF) and daclatasvir (DOC) are suggested for the treatment of hepatitis C virus (HCV) in patients with concomitant HCV and human immunodeficiency virus (HIV). In 2016, Sovodak tablet a combination of SOF and DOC was introduced. In the present study we assessed the effectiveness of SOF in the treatment of HCV in patients co-infected with HIV. Methods: A total of 26 HCV patients co-infected with HIV received SOF for 3 months. One patient did not adhere to the drug protocol and was removed from the final analysis. The blood sample for qualitative polymerase chain reaction (PCR) was obtained after treatment and sustained virological response (SVR) was calculated. Results: Twenty five patients finished the study. The mean patients' age was 44.16±6.21 years. About 72% of participants had HCV genotype 1a, 8% genotype 1b, and 20% genotype 3a. After 3 months of intervention with Sovodak, the SVR12 was about 96%. None of the patients reported any adverse events. Conclusion: For the first time, the results of the present study showed that Sovodak had high SVR12 in HCV patients co-infected with HIV. However, for a precise conclusion, there is a need for larger studies and an equal number of patients with different virus genotypes.

Evaluation of the Methylation of MIR129-2 Gene in Gastric Cancer.

BACKGROUND: Genetic and epigenetic changes have strong role in the development of gastric cancer. The mutation of the MIR129-2 gene is one of the major causes in many cancers, especially gastric cancer. The aim of this study was to investigate the methylation changes of the MIR129-2 gene in tumor and normal tissue of patients with gastric cancer. METHOD: In this study, 50 gastric cancer patients with Iranian Azari ethnic origin without any familial relations were included. Genomic DNAs was extracted from the tumoral and normal tissues. Then the promotor regions of the MIR129-2 gene were analyzed by methylation-specific PCR (MSP) to evaluate the presence or absence of methylated CpG sites. RESULTS: There was a statistically significant difference in methylation level of MIR129-2 gene between tumoral and normal tissues. It was observed that 84 out of 100 CpG cites were methylated in tumoral tissues in compression to 13 out of 100 CpG cites in normal tissues. CONCLUSION: MIR129-2 gene was hypermethylated in tumoral tissues, suggesting that methylation is involved in the development of gastric cancer.

CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients.

PURPOSE: Gastric cancer is an aggressive disease which is the fourth prevalent malignancy in the world. Beside the genetic factors, epigenetic alterations such as promoter CpG island hyper methylation are involved in the emergence of gastric cancer. Herein, we investigated the methylation status of CDH11, EphA5, and HS3ST2 genes in patients with and without gastric adenocarcinoma for the first time. METHODS: In the study 40 paraffin-embedded tissue sections from gastric adenocarcinoma patients and 40 specimens from patients with functional dyspepsia were taken. DNA extraction was performed using a modified salting out method. Epizen DNA methylation kit was used to the bisulfite DNA conversion. The methylation status of CDH11, EphA5, and HS3ST2 genes were analyzed by methylation-specific PCR (MSP) technique. RESULTS: Among the 80 specimens, 71 DNA samples were achieved (34 gastric adenocarcinoma patients and 37 control patients). The results showed that CDH11, EphA5, and HS3ST2 genes are methylated in 28 (82.45%), 19 (55.88%), and 26 (76.47%) of 34 DNA samples from gastric adenocarcinoma patients, respectively, whereas, these genes are methylated in 7 (18.91%), 9 (24.32%) and 7 (18.91%) of 37 samples from noncancerous patients, respectively. Statistical analyses using a chi-squared test showed that there is a statistically significant difference in methylation level of CDH11, EphA5, and HS3ST2 genes between gastric cancer and uncancerous patients (p < 0.05). CONCLUSION: To the best of our knowledge, this is the first report on methylation of CDH11, EphA5, and HS3ST2 promoters' in gastric adenocarcinoma patients using MSP. Identification of novel cancer-related molecular mechanisms can be useful in detection of new treatment strategies.

Turmeric and chicory seed have beneficial effects on obesity markers and lipid profile in non-alcoholic fatty liver disease (NAFLD).

In an attempt to investigate new strategies aimed at reducing risk factors of non-alcoholic fatty liver disease (NAFLD), effects of turmeric (Curcuma longa L.) and chicory seed (Cichorium intybus L.) supplementation was evaluated in these patients. In this double-blind, randomized, controlled clinical trial, 92 patients with NAFLD aged 20-60 year with body mass index (BMI) ranged 24.9-40 kg/m2 was randomly assigned to 4 groups as follows. 1) Turmeric supplementation (3 g/d) (n = 23, TUR); 2) Chicory seed supplementation (infused 9 g/d (4.5 g /100mL)) (n = 23, CHI); 3) Turmeric and chicory seed supplementation (3 g/d turmeric + infused 9 g/d chicory seed (n = 23, TUR + CHI); 4) Placebo (n = 23, PLA). All intervention periods were 12 weeks. Fasting blood samples, anthropometric measurements, dietary records and physical activity were collected at baseline and at the end of the trial. Significant decreases were observed in BMI and waist circumference (WC) of subjects in CHI and TUR + CHI groups, compared with PLA group (p < 0.05). Combination of turmeric and chicory seed significantly decreased serum alkaline phosphatase level (p < 0.05). Serum levels of HDL-C increased considerably in TUR and TUR + CHI groups (p < 0.05 vs. placebo). Turmeric supplementation alone and plus chicory seed led to significant reduction in serum levels of TG/HDL-C and LDL-C/HDL-C ratio in TUR and TUR + CHI groups in comparison with placebo (p < 0.05). In conclusion, turmeric and chicory seed supplementation can be significantly useful in management of NAFLD risk factors.

Expression Level of miR-34a in Tumor Tissue from Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: miR-34a has been shown to be involved in P53 regulation. In this study, we aimed to evaluate the expression level of miR-34a in esophageal cancer and compare it with that of the normal marginal tissues. METHODS: Tumor and marginal tissues were obtained from 50 patients with esophageal cancer. After RNA extraction, expression level of miR-34a was determined using SYBR green master mix and real-time quantitative PCR. RESULTS: It was observed that there was a downregulation of miR-34a in tumoral tissue of esophageal patients in comparison to normal marginal tissues. Moreover, the expression level of miR-34a was correlated with clinicopathological specifications of the patients. CONCLUSIONS: miR-34a may be involved in the pathogenesis and development of esophageal cancer and have the potential to be used as a diagnostic and therapeutic marker in esophageal cancer.

Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial Adenomatous Polyposis - the First FAP registry in Iran

Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited disorder is characterized by the presence of multiple adenomatous colorectal polyps, which can develop into cancer during early adulthood. Therefore, early diagnosis is essential. Most FAP patients have several extracolonic manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE). Whereas genetic markers may provide the main route to detection of ''at risk'' subjects , at present this approach is clearly limited and searches for a noninvasive phenotypic marker continue to be high priority.The aim of this study was to describe the pattern of distribution of CHRPE lesions and evaluate their diagnostic value in FAP patients and their family members in a local population. Methods: A total of 23 FAP patients and 26 relatives belonging to 12 families at high risk of developing FAP were subjected to colonoscopic and ophthalmological examination. Result: Retinal examinations demonstrated prevalences of CHRPE in FAP patents and their siblings of 78% and 38%, respectively. We were able to illustrate a significant correlation between FAP disease and the presence of retinal lesions. Sensitivity and specificity of CHRPE as a screening test to detect the presence of FAP are 78.3% and 61.5%, respectively, with a positive predictive value of 64.3% and a negative predictive value of 76.2 %. A "lesion form" significant difference was found between FAP and normal participants.Spearman nonparametric analysis revealed no correlation between age and number or size of lesions. Conclusion: Multiple CHRPE lesions are a diagnostic feature of FAP patients They are specific and sensitive clinical markers of this disease (specificity 60% and sensitivity 77%).

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran.

BACKGROUND: Colorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients. MATERIALS AND METHODS: This study was conducted on 100 CRC patients by the case-only method. Polymerase chain-reaction products were analyzed by Sanger sequencing, and sequence results were compared with the significant KRAS and BRAF gene mutations in the My Cancer Genome database. Logistic regression models were used to detect associations of clinicopathologic characteristics with each of the mutations. Kaplan-Meier and Cox regression models were constructed to estimate overall survival in patients. RESULTS: A total of 26 subjects (26%) had heterozygote-mutant KRAS, and mutations were not detected in the amplified exon of BRAF in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of KRAS mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of KRAS mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with KRAS wild-type cancers, those with KRAS mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44-9.68; log-rank P=0.003). CONCLUSION: Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease.

The Relation between Left Coronary Dominancy and AtheroscleroticInvolvement of Left Anterior Descending Artery Origin.

INTRODUCTION: Limited information is available regarding the relationship between coronary vessel dominance and atherosclerotic involvement. Rheological factors have been implicated in the pathogenesis of coronary lesions. More than 90% of the coronary blood flow enters the left coronary if it is the dominant artery. The main purpose of this study was to determine the relation between left coronary dominance and atherosclerotic involvement of left anterior descending artery (LAD) origin. In addition, the prevalence and degree of associated ischemic mitral regurgitation (MR) in these patients were assessed. METHODS: The study included 678 consecutive patients with an indication for coronary angiography. One hundred and twenty two patients with right dominant and 61 patients with left dominant arteries were randomly selected for analysis. All demographics, risk factors, coronary dominancy and involvement, left ventricular ejection fraction (LVEF), and MR were recorded. RESULTS: One hundred and eighty three patients (mean age of 57.7 years) were studied. The types of coronary circulation included right, left, and balanced in 78.6%, 8.9%, and 12.5%, of the patients respectively. In 64 patient with significant LAD lesions, 22 (34.9%) had ostial while the remainder had non-ostial involvement. Ischemic MR was present in 5 (2.7%) patients. There was no difference in demographics, risk factors, LVEF, MR, extent of coronary artery disease, and LAD ostial involvement between left and right dominant circulations. CONCLUSION: In this study, left coronary dominance was not associated with atherosclerotic involvement of LAD ostium and ischemic MR.

Pseudoaneurysm of the portal vein as a rare source of gastrointestinal bleeding in pregnancy: a case report.

A 28-year-old, 32 week pregnant primigravida woman with a past history of increased blood pressure presented with RUQ pain as well as sudden onset of hematemesis. This case illustrates the occurrence of a rare complication (rupture of portal vein pseudoaneurysm inside the biliary system), appearing as upper gastrointestinal bleeding in a pregnant woman. The cause of the rupture is presumably pregnancy-related. We would like to emphasize the presence of pseudoaneurysm of the portal vein as a rare source of gastrointestinal bleeding in pregnancy.