Review Article

The CpG island methylator phenotype (CIMP) in colorectal cancer

Ehsan Nazemalhosseini Mojarad, Peter JK Kuppen, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):120-128

It is clear that colorectal cancer (CRC) develops through multiple genetic and epigenetic pathways. These pathways may be determined on the basis of three molecular features: (i) mutations in DNA mismatch repair genes, leading to a DNA microsatellite instability (MSI) phenotype, (ii) mutations in APC and other genes that activate Wnt pathway, characterized by chromosomal instability (CIN) phenotype, and (iii) global genome hypermethylation, resulting in switch off of tumor suppressor genes, indicated as CpG island methylator phenotype (CIMP). Each of these pathways is characterized by specific pathological features, mechanisms of carcinogenesis and process of tumor development. The molecular aspects of these pathways have been used clinically in the diagnosis, screening and management of patients with colorectal cancer. In this review we especially describe various aspects of CIMP, one of the important and rather recently discovered pathways that lead to colorectal cancer.

Original Article

The effect of 5´untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer

Vahid Chaleshi, Mahdi Montazer Haghighi, Gholam Reza Javadi, Seyed Reza Fatemi, Mohsen Vahedi, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):129-135

Aim: The purpose of this study was to determine the relationship of rs4444903 (EGF+61A/G) SNP genotype with colorectal cancer and tumor stage in an Iranian population.

Background: Epidermal growth factor (EGF) is one of the important proteins that determine survival of cells. EGF binds to its receptor on the cell surface and then activates some of the cell signaling pathway networks within cells that lead to activation or deactivation of factors which are responsible for growth and apoptosis of cells. In this study we assessed the association in EGF polymorphism rs4444903 with colorectal cancer (CRC) in Iranian population.

Patients and methods: We conducted case-control study to investigate the association of polymorphism rs4444903 in EGF, with colorectal cancer risk in Iranian population. Analyzed Polymorphism of EGF rs4444903 with restriction fragment length polymorphisms (RFLP) among two groups of subjects consisting of including 220 cases with colorectal cancer and 220 healthy individuals as controls. Mutations were confirmed in 10% of the samples by direct sequencing.

Results: The frequencies of AA, AG and GG genotypes among cases with colorectal cancer were 28.2, 46.8, and 25.0 % respectively and in controls genotype frequencies were 23.2, 56.4, and 20.5 %, respectively. Frequency of A allele among case group was 51.6% and for control group was 51.4%. The frequency of G allele in case and control was, respectively 48.4% and 48.6% (OR= 1.009, 95% CI= 0.775-1.315; P= 0.946). The percentage of Stage 0, I, II, III, IV were 5%, 9.35%, 38.84%, 30.21% and 16.54%, respectively, among the cases. However, no significant association between this polymorphism and CRC stage was observed (p=0.626).

Conclusion: Our data suggest a SNP rs4444903 may not represent a risk factor in the development and progression of CRC among Iranian population.

Epidemiological features of hepatitis B and C infection in a high risk population: results of screening programs

Simin Noori, Ali Gol-Mohamadi, Mohammad Reza Sarbazi, Azadeh Safaee, Ahmad Reza Farsar

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):136-140

Aim: The aim of this study was to report the epidemiological features of HBV & HCV infection in an Iranian high risk population.

Background: Hepatitis B and hepatitis C infections are worldwide serious public health problems. Iran has an intermediate prevalence of infection and a screening program was started in 2010 among high risk individuals.

Patients and methods: This cross-sectional study was conducted on 4455 new patients during two past years. Demographic information, age, gender, occupational status, medical history, history of vaccination against HBV, high risk exposure and laboratory findings were collected for each patient. Then distribution of demographic and risk factors was evaluated in each type of hepatitis.

Results: The mean age of patients was 45.6±17.3 years. More than two-thirds of the diagnosed cases were infected with HBV. 74% of patients were carriers of hepatitis virus. 60% of patients had no symptoms at diagnosis. Illicit intravenous drug use was most common high risk exposure in patients under study (n=366, 8.2%). High risk behaviors including illicit intravenous drug use and unprotected sex were relatively higher in patients infected with hepatitis C compared to patients with hepatitis B infection.

Conclusion: Findings of this study suggest that illicit intravenous drug use, contact with an infected household member and unprotected sex are the most common high risk exposure in Iranian patients infected with viral hepatitis. Therefore, preventive strategies such as health education, vaccination and screening programs should be directed to these groups. The results also show that a majority of patients have no symptoms at the time of diagnosis, therefore periodic screening tests in high risk groups is required.

Evaluation of the benefit of addition of clidinium C to a Helicobacter pylori eradication regimen

Maryam Chorami, Homayoun Zojaji, Nosratollah Naderi, Bijan Moghimi-Dehkordi, Dariush Mirsattari, Hamid Mohaghegh Shalmani

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):141-145

Aim: This study aimed to evaluate the success of H.pylori eradication therapy in patients with dyspepsia by therapeutics regimes with and without clidinium C.

Background: Helicobacter pylori infections are reported in all parts of the world. Appropriate antibiotic therapy can treat infection. The ideal treatment regimen has not been specified.

Patients and methods: In a randomized, double blind clinical trials study, 250 patients with dyspepsia were enrolled. All patients were treated by Omeprazole, Metronidazole, Amoxicillin and Bismuth (OMAB) for two weeks. One tablet clidinium C before each meal was added to this regimen in the intervention group (A). Urea Breath Test (UBT) was carried out after 8-12 weeks after treatment for evaluation of H.pylori eradication.

Results: 132 patients in the intervention group (A) and 118 patients in the control group (B) were enrolled to the study. The rate of eradication in group A was significantly higher than group B (62.1% vs. 50%, p=0.04).

Conclusion: The results supported the effect of clidinium C for increasing of helicobacter pylori eradication, but further studies need to be performed.

Study on association between H-ras gene polymorphism and gastric adenocarcinoma risk

Masoumeh Rostami, Zahra Kalaei, Mohamad Amin Pourhoseingholi, Mehdi Kadivar

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):146-151

Aim: The aim of this study was to investigate relation between H-ras T81C polymorphism and some of the important risk factors in gastric adenocarcinoma (GA).

Background: GA is one of the leading causes of cancer death in most countries. RAS gene is an important member in the PI3K-AKT signaling and the single nucleotide polymorphism at H-rasc DNA position 81 has been demonstrated has an important role in tumor genesis.

Patients and methods: In this study, we carried out single-nucleotide polymorphism analysis in an Iranian population. A total of 100 patients with gastric adenocarcinoma and 100 controls were examined for the presence of T81C H-ras polymorphism using PCR- RFLP assay.

Results: Statistical analysis revealed no relationship significant between TT, TC, CC and risk of GA, but, there was a poorly relation between male patient with C-carrier genotype and increasing risk of GA (P=0.07). Also, we investigate effect of four important risk factors for GA. There was a statistically significant difference between increasing of age and susceptibility for GA (OR=1.106, 95%CI=1.073-1.139, P<0.001). We observed a statistically significant between smoking and T81C polymorphism C-carrier genotypes (OR=3.98, 95%CI=1.831-8.68, P<0.001) as this individual had three-time risk for GA. We did not show a significant association between three main genotypes and H. pylori infection for risk of GA.

Conclusion: These results suggested that there is no relationship between T81C-HRAS polymorphism and gastric cancer risk in Iranian patients. But, gender (male in our study) and the other risk factor described above have an important role in developing of GA.

New features of fascioliasis in human and animal infections in Ilam province, Western Iran

Jahangir Abdi, Razi Naserifar, Mohammad Rostami Nejad, Vahid Mansouri

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):152-155

Aim: The aim of this study was to investigate the prevalence of human and animal fascioliasis in Ilam Province, Iran.

Background: Fascioliasis, caused by Fasciola hepatica, is one of the most important zoonotic diseases. Snails are an intermediate host. Human infection with the parasite can led to hypertrophy and hyperplasia in bile duct. It also economic importance and further information is essential about the epidemiology of the parasite in Ilam province.

Patients and methods: The study on animals was descriptive and retrospective. All records from abattoirs were analyzed. It was conducted on 27242 indigenous animals including 17055 sheep, 5703 goats, and 4484 cattle. For the study of human Fascioliasis infection 600 human sera, from person among 5-80 year old, were collected and ELISA test was used for identification of IgG antibody to Fasciola hepatica by commercial kit.

Results: The overall prevalence of Fasciola hepatica among 27242 slaughtered animals was 0.98%. Out of 267 domestic animals, 98 sheep, 28 goats and 141 cattle were infected with the parasite. The highest and lowest infection rate of 3.14% and 0.1% were cattle and goat, respectively. The prevalence of IgG antibody was0.66% (n = 4) against Fasciola hepatica in humans. Three infected people were living in rural areas. The highest infection rate (3 people) was found in women.

Conclusion: Ilam province is among the areas where the prevalence of Fasciola hepatica is low. This is probably due to the drought in the region in recent years that makes conditions difficult for the survival of snails, the intermediate hosts. But there is a risk of the disease increasing in incidence, in this region.

Case Report

Perforated jejunal diverticula- a rare cause of acute abdominal pain: a case report

Mohammad Esmail Akbari, Khashayar Atqiaee, Saran Lotfollahzadeh, Amir Naser Jadbbaeey Moghadam, Mohammad Reza Sobhiyeh

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):156-158

Jejunal diverticula have a prevalence of approximately 1% in the general population. Perforation of jejunal diverticulum is a rare. Clinically this diagnosis may be easily confused with other causes of an acute abdomen. In the article, we discuss a 74-year–old man with a 2-day history of constipation and left–sided abdominal pain. The day before admission he developed an abrupt exacerbation his symptoms with pain localized to periumbilical and left lower quadrant. An abdominal computed tomography scan revealed soft tissue stranding within the left upper quadrant, bilateral plural effusions , larger on the left, an opacity with the right and left pulmonary lobes and polypoid lesion with in stomach.

Physical examination revealed left upper quadrant fullness. An emergency laparotomy was carried out. This revealed multiple jejunal diverticula, one of which had perforated 40 centimeters distal to the ligament of Treitz.

A patient with cystic lymphangioma in pancreas

Afshin Moradi, Mohammad Reza Sobhiyeh, Sayena Jabbehdari, Behzad Azimi, Saran Lotfollahzadeh, Nazli Sadeghi, Nafisseh Jafarian

Gastroenterology and Hepatology from Bed to Bench, Vol. 6 No. 3 (2013), 9 Khordad 2013, Page Gastroenterol Hepatol Bed Bench 2013;6(3):159-164

Cystic lymphangioma of the pancreas is extremely rare, accounting for less than 1% of pancreatic tumors. Though congenital, it can affect all age groups. Cystic lympangioma occurs more frequently in females. Patients usually present with epigastric pain and an associated palpable epigastric mass. Complete excision is curative, even though, depending on the tumor location, surgery may be simple or involve extensive pancreatic resection and anastomoses. In this case report, we discuss a 63-year old patient who presented with epigastric pain and on investigation was found to have pancreatic head cystic lymphangioma. At surgery the tumor was completely excised, with preservation of pancreatic duct. Histology and immunohistochemistry confirmed cystic lymphangioma of the pancreas. This case highlights that a diagnosis of cystic lymphangioma of the pancreas should be taken into consideration as a differential diagnosis of pancreatic cystic lesions.

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