Is the Presence of Helicobacter Pylori in the Colonic Mucosa, Provocative of Activity in Ulcerative Colitis?

Background: Epidemiologic studies have shown world-wide increasing incidence of ulcerative colitis (UC) as an autoimmune disease of intestine. In the meantime, gastrointestinal H. Pylori infection is being decreased. Objectives: There are very few studies about comparing the presence of H. Pylori in the colon and the disease activity of UC. There is no study form Iran. In this study, we tried to investigate the presence of H. Pylori in the mucosa of colon by molecular and microbiological as well as pathological methods to find any association between the presence of this organism in the colon and the presence and activity of UC. Patients and Methods: In 100 patients who referred to colonoscopy clinic, colonoscopy was performed. Fifty-seven patients with the new diagnosis of UC were considered as cases and 43 patients with normal screening colonoscopy for polyps were considered as controls. Colon biopsies were evaluated according to histopathology, clinical findings, and laboratory results to confirm the diagnosis and the degree of activity in the cases of UC. Molecular studies were also performed to evaluate the presence of H. Pylori genome in the colon biopsies. A sample of colon was also cultured for H. Pylori. ELISA test was performed in a sample of blood to evaluate the level of IL-10 and IL-17 as regulatory cytokines of inflammation. Results: Cases with the diagnosis of UC showed significantly higher number of positive colonic H. Pylori comparing to normal colonic mucosa. Also, the presence of H. Pylori genome in the colon was associated with higher activity in the cases with UC and higher levels of inflammatory mediators especially IL17 and lower levels of inhibitory mediators such as IL-10. Conclusion: Colonic colonization of H. Pylori was higher in the patients with UC and higher activity of this disease comparing with normal control colonic mucosa.

Microsatellite Instability and Colorectal Cancer, Immunohistochemical and Molecular Evaluation by Using DNA Sequencing: A Single Center Experience.

BACKGROUND & OBJECTIVE: Microsatellite instability is common in familial colorectal cancers. It can be tested by the molecular and immunohistochemical methods. There are very few studies which address comparing the clinicopathological characteristics of microsatellite stable (MSS) and microsatellite unstable (MSI) colorectal cancers from Iran. In this study, we aimed to evaluate the clinicopathological and immuno-histochemical findings of MSS and MSI colorectal cancers in our Center as the largest Center of gastrointestinal surgery and oncology in the South of Iran. We also compared the immunohistochemical method vs. molecular study using DNA sequencing. METHODS: For 5 years (2015-2019), 34 patients who underwent operation in the affiliated Hospitals of Shiraz University of Medical Sciences were clinically suspected to microsatellite instability (MSI). The molecular diagnostic tests with DNA sequencing were performed. Clinicopathological and immunohistochemical findings of MSI colorectal cancers were compared with those who were stable. RESULTS: In the South of Iran, MSI colorectal cancers were more common in males. These tumors were more common in the right side with more tendencies to produce mucin with lymphocytic infiltration. CONCLUSION: Immunohistochemistry would be a specific method for diagnosis of MSI colorectal cancers but may be associated with high rate of false negative results and of low sensitivity. Therefore, we recommend performing molecular studies by DNA sequencing in those colon cancers with clinical suspicion for MSI and negative immunohistochemical findings.

Epidermal Growth Factor Receptor (EGFR) Gene Mutation Analysis in Adenocarcinoma of Lung, the First Report from Iran.

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about the frequency of the EGFR mutation in lung adenocarcinoma, yet molecular study about this incidence has been published from Iran. In this study, we investigated the frequency of this mutation in our center, which is the largest referral center in the south of country. This report will be the first published article about EGFR mutational analysis from Iran. METHODS: During the study period (September 2011 till September 2016) i.e. 5 years, there have been 50 cases of pathologically-confirmed lung adenocarcinoma. These cases underwent mutational analysis for exons 18 to 21 of the EGFR gene by PCR and DNA sequencing. All demographic findings were also extracted from the patients' charts and recorded. RESULTS: There were 30 male and 20 female patients, with an average age of 58 years. The overall frequency of EGFR mutation was 28% (14 out of 50). The most common mutation was Del 19 (10 of 14, 71.4%), 3 mutations were found in exon 20 and one mutation was found in exon 21. EGFR mutations were more frequent in women than in men (30% versus 26.7%) and in nonsmokers than in smokers (37.9% versus 14.3%). CONCLUSION: Lung adenocarcinoma with EGFR mutation shows strong association with female non-smokers. Our results showed an intermediate frequency of this mutation, which was higher than results from Western countries and lower than most Asian countries.

Frequency of NRAS Gene Mutation in Wild Type KRAS and BRAF Colorectal Cancers; a Single Center Study.

BACKGROUND Incidence of colorectal cancer is increasing in countries such as Iran. Molecular biomarkers play very important role in the diagnosis, treatment, and prognosis of this cancer. Mutation in the RAS family (including KRAS and NRAS) is one of these important molecular biomarkers, which should be tested before starting treatment with anti-EGRF (Epidermal growth factor) drugs. Objectives: There has been very few reports about the frequency of NRAS mutation from Iran and no study from south of the country. In this article we will describe our experience about the frequency of NRAS mutation in colorectal cancers from the largest referral center in the south of Iran. METHODS During 5 years (2011-2015), we had 52 cases of colorectal cancers with wild type KRAS and BRAF in the hospitals affiliated to Shiraz University of Medical Sciences with enough tissue for molecular studies. NRAS mutation analysis was performed on paraffin embedded formalin fixed tissue of these cases by polymerase chain reaction (PCR)-sequencing method. RESULTS Among these 52 cases of colorectal cancer with wild type KRAS and BRAF, there has been 3 (5.7%) cases with mutant NRAS. One of the mutations has been in codon 12 and two in codon 61. No mutation in codon 13 was found. All the three cases were women with stage IV and well differentiated histomorphology. CONCLUSION Our results showed that frequency of NRAS mutation in colorectal cancer is rare, which is very close to other studies from different geographic areas of the world.

K-ras Mutation in Colorectal Cancer, A Report from Southern Iran.

There are very few studies about K-ras mutations in colorectal cancer (CRC) from developing countries such as Iran. It is therefore essential to conduct studies to learn about the molecular signature of such tumors, allowing the determination of an appropriate management plan. In the present study, we aimed to determine the frequency and types of K-ras mutations among patients with CRC in Iran. Formalin-fixed paraffin-embedded specimens of 100 cases of CRC were collected from hospitals affiliated with Shiraz University of Medical Sciences (June 2011 to June 2013). All of the H&E slides were examined and proper slide with a minimum of necrosis and maximum of well-preserved tumor cells (at least 70% tumor in each slide) were selected. Recurrent, metastatic, and post chemotherapy cases were excluded from the study. Mutation of codons 12 and 13 of K-ras gene by PCR was performed, followed by direct sequencing by Sanger method. From 100 eligible cases (55 male and 45 females with mean age of 59 years), 32% had mutant K-ras gene; the most common substitution was 12G>C followed by 12G>A and 13G>A, respectively. It is found that K-ras mutation rate, among the selected population of the southern province of Iran, was as high as 32% (codon 12: 71.8% and in codon 13: 25% and one in both codons: 3.1%).

Low Incidence of α-1 antitrypsin deficiency among babies with prolonged jaundice.

UNLABELLED:   BACKGROUND: α-1 antitrypsin (AAT) deficiency is one of the most important genetic causes of childhood liver diseases in some parts of the world, but its geographic distribution is highly variable. There are many reports from Asian countries such as India, the Philippines, and China which show a very low incidence of this disease. However few studies exist from Iran regarding this genetic deficiency as the cause for prolonged neonatal jaundice. In this study we attempt to investigate the possible role of AAT deficiency as a cause of prolonged neonatal jaundice in the largest pediatric referral center of Southern Iran. METHODS: We included 126 neonates with the clinical diagnosis of neonatal cholestasis in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the extracted DNA from their blood samples. DNA sequencing confirmed the results of the PCR-RFLP tests. RESULTS: All patients were genetically normal regarding level of AAT, i.e., all were MM homozygotes. CONCLUSION: AAT deficiency is a rare disease in Iran and is not a major cause of neonatal cholestasis in this country.