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BACKGROUND Hepatitis C virus (HCV) is considered to be the major cause of post-transfusion hepatitis in patients with thalassemia. We aimed to determine the HCV prevalence, genotypes, and viral load among patients with major β-thalassemia in Mashhad, Iran. METHODS Medical records of all 550 patients with major β-thalassemia who referred to ThalassemiaHemophilia Center of Mashhad (Sarvar Clinic) were reviewed from October to November 2011. Plasma samples of the patients were tested for the presence of anti-HCV antibodies by enzyme linked immunosorbent assay. Real-time polymerase chain reaction (PCR) was used to determine viral genotype and HCV RNA titer. RESULTS HCV antibodies were detected in 37 individuals (6.73%) including 17 men and 20 women with mean age of 25.2 ± 8.4 years. The PCR analysis was performed for 27 patients, of whom HCV RNA was detected in 17 patients (63.0%). Viral titers were investigated in 14 subjects and a high viral load more than 600000 copies/mL was observed in 6 patients (42.9%). The most prevalent genotypes were 3a (50.0%) followed by 1a (37.5%). No significant correlation was found between genotype and age, sex, serum ferritin, liver tests, and HCV RNA titer. CONCLUSION HCV infection among patients with thalassemia is more common than general population in Mashhad, northeast Iran. The dominant HCV subtype is 3a followed by 1a. These findings could help health authorities to provide preventive measures, and practitioners to choose the right protocol of treatment for the patients., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work.

Competing Interests: All authors declare no conflicts of interests.

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide. It is the most common histological type of esophageal carcinoma in low-resource countries. ESCC is prevalent in Asian countries, accounting for more than 95% of esophageal cancers. The epidermal growth factor receptor (EGFR) is involved in cancer development, as its gene is often mutated and/or amplified in cancer cells. According to recent statistics, esophageal cancer is the eighth most common cancer in Iran., Methods: In this retrospective study, we assessed EGFR overexpression, using immunohistochemistry (IHC) in 68 patients with ESCC, undergoing neoadjuvant chemoradiotherapy and esophagectomy in 2011-2014. The treatment protocol included external beam radiotherapy (40 Gy), concomitant with cisplatin 20mg/m2 and 5- fluorouracil (5-FU) 1000 mg/m2 for 4 consecutive days during the first and fourth weeks of treatment. To compare the two groups (EGFR positive and negative) in terms of complete pathologic response, Chi-square test was performed using SPSS version 16., Results: The median age of the patients was 59 years (range: 27-70 years), with a female-to-male ratio of 1.06. Overall, 70% of the subjects showed EGFR overexpression. Complete pathologic response to neoadjuvant treatment was significantly higher in EGFR-positive patients (40% vs. 15.8%, P = 0.05). In all cases, 1- and 3-year overall survival rates were 86.6% ± 4.1 and 48% ± 6.9, respectively. The 1- and 3-year disease free survival rates were calculated as 71.8% ± 5.4 and 44.3% ± 6.5, respectively. The overall survival rate was relatively higher in cases with EGFR overexpression, although the difference was not statistically significant (5-year survival rate: 47.9 ± 8.2 vs. 30.9 ± 13, P = 0.23)., Conclusion: EGFR overexpression was reported in the majority of patients with ESCC in northeastern Iran. Moreover, EGFR overexpression was significantly associated with complete pathologic response.

Aim: To describe our experience using a low-accelerating-dose regimen (LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus (HCV) recurrence., Methods: From 2003, a protocolized LADR strategy was employed to treat liver transplant (LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B (rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include (1) patient and graft survival; (2) effect of anti-viral therapy on liver histology (fibrosis and inflammation); (3) incidence of on-treatment development of ACR, CDR, or PCH; (4) association of recipient and donor IL28B genotype with SVR; and (5) incidence of anti-viral therapy-associated adverse events (anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation., Results: The overall SVR rate was 38% (29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt (P < 0.0001), donor age (P = 0.003), cytomegalovirus mismatch (P = 0.001), baseline serum bilirubin (P = 0.002), and baseline viral load (P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs (P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR (97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L (P = 0.01), total bilirubin ≥ 1.5 mg/dL (P = 0.001) and creatinine ≥ 2 mg/dL (P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the follow-up period. Treatment discontinuation and treatment-related mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six (25%) of the patients were deceased; among those who died, 25 (54%) were due to liver-related complications, and 4 deaths (9%) occurred while receiving therapy (2 patients experienced hepatic decompensation and 2 sepsis)., Conclusion: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.

Primary sclerosing cholangitis (PSC) is typified by a heterogeneous histology with periductal fibroinflammatory lesions. The hepatic arterioles in PSC have not been well characterized. Using image analysis, we sought to examine the dimensions of hepatic arterioles in PSC. We identified 30 livers from patients transplanted for PSC as well as 10 explants each from cirrhotic patients (serving as controls) having primary biliary cirrhosis, hepatitis C (HCV), and alcoholic liver disease. At least two representative hematoxylin and eosin-stained slides were selected, and ten cross-sectioned hepatic arterioles were photographed for image analysis. The vessels were measured at their longest span and width based on the outer portions of the tunica media. Wall thickness was measured at its thickest portion from the intima to the outer portion of the tunica media; the perimeter of the luminal area was outlined by the endothelial lining, generating the total luminal area. Mean arteriolar length, width, and wall thickness (p = 0.012, p = 0.004, p = 0.001, respectively) were greater in the PSC group; luminal area was similar between the groups. When compared to the individual sub-groups, wall thickness of arterioles in PSC remained significantly greater. End-stage PSC has even larger-sized arterioles and greater wall thickness as compared to that of other cirrhotic livers. This increased wall thickness found in PSC cannot be solely attributed to cirrhosis itself. These vessel changes may potentially be the result of, or contribute to, the pathogenesis of PSC.

Purpose: Gastric cancer is the second leading cause of cancer-related deaths worldwide and the most common gastrointestinal cancer in Iran. Chemokine ligand 5 (CCL5/RANTES) is one of the most potent angiogenic factors that plays an important role in tumor growth, invasion, and metastasis. We aimed to assess the serum level of CCL5 in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prognosis., Methods: Seventy-four patients with gastric adenocarcinoma that had undergone gastrectomy and 96 non-tumoral cases in which gastric cancer was ruled out by gastroscopy and biopsy were enrolled. Demographic and epidemiological characteristics and patient survival data were reviewed. Histological type, grade, and tumor stage (TNM) were determined by a single expert pathologist. Helicobacter pylori infection status and CCL5 serum level were measured by ELISA. Data were analyzed using SPSS software version 16., Results: Patients with gastric adenocarcinoma had significantly higher serum CCL5 level compared with control group (P < .001). Higher serum CCL5 levels were associated with lower histological differentiation (P < .001), higher depth of tumor invasion (P = .022), more frequent lymph nodes involvement (P = .028), and advanced tumor stage (P = .002). The overall survival of patients with CCL5 levels higher than 70,671 pg/ml was significantly lower than those with lower than this cutoff (P = .043)., Conclusions: Serum CCL5 levels might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma. Further studies to assess tissue expression of CCL5 and its gene polymorphisms are suggested.

Context: The incidence of obesity is increasing and contributes to the rising incidence of fatty liver. Body mass index (BMI) is used to assess the degree of obesity but does not take into account the pattern of body fat distribution., Objectives: To confirm the increasing incidence of fatty liver in an autopsy study. We hypothesized that a standardized measurement of abdominal subcutaneous adipose tissue (ASAT) might be a good noninvasive method for differentiating steatohepatitis from steatosis., Design: Consecutive complete adult postmortem cases were studied and liver sections were assessed with a steatohepatitis scoring system. Spleen weight, ASAT, and clinical information were obtained. Spleen histology was assessed in a subset of patients having splenomegaly in the absence of cirrhosis., Results: Patients with human immunodeficiency virus, hepatitis C virus, and appreciable alcohol use were excluded. Of 306 cases, the frequency of fatty liver was 51.6% with 33.3% having simple steatosis and 18.3%, having steatohepatitis. Mean ASAT was 3.7 cm in the steatohepatitis group versus 2.6 cm in the steatosis group (P < .001); this difference was greater in patients with a BMI less than 25 kg/m(2) (P = .05). Fibrocongestive splenomegaly was noted in 9 of 38 patients with nonalcoholic steatohepatitis (24%) in the absence of cirrhosis., Conclusions: In this series of autopsy cases, a dramatic increase in the prevalence of fatty liver disease is demonstrated. Thicker ASAT is associated more with steatohepatitis than with simple steatosis, especially in patients with BMI below 25 kg/m(2). Fibrocongestive splenomegaly may occur in the absence of cirrhosis in the presence of steatohepatitis.

Background: Hepatitis C virus (HCV) infection is a significant health problem throughout the world. Chronic form of the disease is found in about 75% to 85% of the newly infected individuals. The chronic infection may lead to severe forms including chronic liver disease, cirrhosis and with a higher mortality rate, hepatocellular carcinoma. Since no vaccine has yet been developed against HCV, there is an increasing need to take measures to control the spread of the infection. Therefore, epidemiologic study of the virus is important to manage and monitor the spread of the virus in the community., Objectives: The aim of this study was to determine the prevalence of hepatitis C seropositivity in the general population of Mashhad, northeast of Iran., Patients and Methods: Three thousand, eight hundred and seventy (3870) individuals living in the city of Mashhad were recruited using cluster sampling method. HCV seropositivity was determined with HCV antibody detection ELISA kit and was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) method., Results: In this study the overall seroprevalence of hepatitis C was founded to be 0.2% by using ELISA method. However, the overall Hepatitis C virus infection prevalence was found to be 0.13% with RT-PCR method., Conclusions: Our study suggested that the prevalence rate of Hepatitis C virus is below 1% in the general population of Mashhad.

Introduction: INF- α is a common drug for the treatment of hepatitis B and C. Although a variety of related complications are discussed, possible ototoxic effects of this mediation are not well described., Methods and Materials: In a before-after control study, 24 patients who received INF- α for the treatment of hepatitis B and C and 30 normal controls were included. Subjective and objective ototoxicity evaluations via questionnaire, high frequency audiometry, and measuring transiently evoked otoacoustic emissions (TEOAEs) were performed one week before and one month after the prescription of the drug. Results. Subjective hearing complaint, tinnitus, and vertigo were seen in just 3 cases, which was not statistically significant (P = 0.083). In the frequency range of 4000 to 8000 Hz before (9.38 ± 1.0 and 10.7 ± 1.2, resp.) and after (17.9 ± 2.6 and 17.6 ± 2.6, resp.) one month of treatment, a significant difference (P = 0.083) was detected. Progressive decreases in amplitude of the OAE during TEOAE measurement in 1, 2, and 4 frequencies among 41.66%, 18.75 %, and 43.75% were observed, respectively. The hearing loss was seen more among older and male cases significantly. Conclusion. The results showed ototoxicity of INF- α that may encourage planning hearing monitoring in patients receiving this drug.

Background: Hepatitis B virus (HBV) infection is a significant health problem throughout the world., Objectives: We aimed to evaluate the prevalence of hepatitis B antigen (HBsAg) seropositivity in the general population of Mashhad, northeast of Iran., Patients and Methods: One thousand six hundred fifty-two healthy individuals aged 1 to 90 (Mean; 29.1 ± 18.5) from all 12 municipalities of Mashad were selected randomly by multistage cluster sampling. Informed consent was obtained, and demographics and medical histories were collected. Twice-reactive samples were considered HBsAg-positive by ELISA. Chi-square test and logistic regression were applied to analyze the factors related to HBsAg positivity using SPSS 16.0., Results: The overall prevalence of HBsAg positivity was 1.39% (95% CI, 0.91% to 2.12%); 2.0% and 0.89% among men and women, respectively (p = 0.054). Infection was more prevalent in older (p = 0.019) and married persons (p = 0.001), Afghanis (p = 0.046), and those with a history of traditional cupping (p = 0.005). There was no association between HBV infection and gender; literacy; income; employment; family size; or history of blood transfusion, dental procedure, surgery, hospitalization, or tattooing. By logistic regression analysis, age was the only variable that had a significant association with infection (p = 0.026)., Conclusion: It seems that the prevalence of HBV infection in Mashhad is slightly lower than that of the nation.

Aim: Based on previous investigations, the progress of gastritis may lead to gastric carcinomas. In some epithelial tumors, macrophage migration inhibitory factor (MIF), which is an inflammatory cytokine may inactivate p53 and play a role in tumorigenesis process. We decided to evaluate clinicopathological significance of MIF expression and the relation between p53 and MIF expressions in gastric adenocarcinomas., Methods: Seventy-three consecutive cases of gastric adenocarcinomas, the tissue samples of which were available, were included in this study. Tissue sections were stained for MIF and p53 expression by immunohistochemistry and the expression was defined as positive (for more than 10%) and negative (for less than 10%) groups. Location of the tumor, histological subtypes, and grade of the tumor were determined by using routine H&E staining. Distant metastasis, lymph node involvement, and consequently the stage of tumor were specified. The patients' age and gender were obtained from their medical records. The relationship between expression of MIF and these variables was determined., Results: Overexpression of MIF was observed in the cytoplasm of cancer cells in 46.6% (34/73) of cases and nuclear immunostaining of p53 was observed in 37% (27/73) of cases. Expression of MIF was significantly correlated with the location of tumor, but this expression has no statistically significant correlation with variables including: age, gender histological subtypes, distant metastasis, and lymph node involvement, stage and grade of the tumor, and p53 tumor suppressor gene expression., Conclusions: Our study suggests that MIF in gastric adenocarcinomas versus many other epithelial tumors cannot have a prominent role in tumor progress and inactivation of p53 tumor suppressor gene.

Pistachio (Pistacia vera) is a tree nut that has been reported to cause IgE-mediated allergic reactions. This study was undertaken to investigate the distinctions between different cultivars of pistachio nut and the influence of different processing on the IgE-binding capacity of whole pistachio protein extracts. The influence of different processes on allergenicity was investigated using competitive inhibition ELISA and Western blotting assays. The Western blotting results of extracts from pistachio cultivars showed no marked difference among them. The IgE-binding capacity was significantly lower for the protein extract prepared from steam-roasted than from raw and dry-roasted pistachio nuts. The results of sensory evaluation analysis and hedonic rating proved no significant differences in color, taste, flavor, and overall quality of raw, roasted, and steam-roasted pistachio nut treatments. The most significant finding of the present study was the successful reduction of IgE-binding by pistachio extracts using steam-roast processing without any significant changes in sensory quality of product.

Background: Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics., Methods: Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay., Results: Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 +/- 63.71 (pg/ml) vs. 92.98 +/- 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 +/- 0.04 (pg/ml) vs. 0.150 +/- 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (N0) showed significantly higher serum levels of sFas compared to others (P = 0.044)., Conclusions: Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.

Background: A complex of genetic and environmental factors is involved in carcinogenesis of the esophageal squamous cell carcinoma (ESCC). Glutathione-S-Transferases (GSTs) are phase-II enzymes playing role in detoxification of carcinogen electrophiles. Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 in association with some environmental factors and their impact on esophageal cancer susceptibility were assessed in the Iranian population., Methods: Genomic DNA of peripheral blood leukocytes from 148 confirmed esophageal cancer cases and 137 healthy individuals as control group was assayed for restriction fragment length polymorphisms in the GSTP1 loci by PCR amplification followed by digestion with Alw26I. Deletion of the GSTM1 and GSTT1 genes was detected by multiplex PCR. A data-mining method based on decision trees was applied to produce a predictive model of interactions between genotypes., Results: Smoking was independently associated with ESCC (p<0.05, OR: 2.286, 95% CI=1.311-3.983). Smoking along with GSTP1 Val/Val genotype was associated to ESCC (p<0.001, OR: 3.886, 95% CI=1.830-8.251), while non-smokers with GSTP1 Val/Val were significantly more frequent in non-cancerous group. (p=0.007, OR: 0.507, 95% CI=0.309-0.830)., Conclusions: Data-mining methods are useful tools to map out a scheme for predicting complex relations and combinations of different genotypes. Genotyping analysis of GSTP1 together with assessment of smoking seems to be important in determining the risk of ESCC in the Iranian population., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types., Methods: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin and eosin (HE) staining was used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test., Results: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P=0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P=0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P=0.008); and this was more prominent in the intestinal (P=0.001) rather than diffuse type., Conclusion: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.

Aim: To determine p16 promoter hypermethylation in gastric tumoral tissue and serum samples, its impact on p16-protein expression, and correlation with clinical and histological features., Methods: Samples were obtained from 52 histologically confirmed cases of gastric adenocarcinoma. Gastric tissue and serum of 50 age- and sex-matched individuals with normal gastroscopy and biopsy were obtained as control samples. Methylation-specific polymerase chain reaction (MSP) was used to evaluate methylation status of p16 promoter. p16-protein expression was analyzed by immunohistochemical staining on paraffin-embedded sections., Results: Methylation was detected in 44.2% (23/52) of tumoral tissues. 60.9% of them were also methylated in serum, i.e., 26.9% of all patients (14/52). Methylation was not detected in tissue and sera of control samples. p16-protein expression was decreased in 61.5% of cases (32/52), and was significantly associated with promoter hypermethylation (P < 0.001). Methylation was significantly more frequent in higher pathological grades (P < 0.05). Methylation was not associated with other clinicopathological features and environmental factors including H pylori infection and smoking., Conclusion: p16 promoter hypermethylation is an important event in gastric carcinogenesis. It is the principle mechanism of p16 gene silencing. It is related to malignant tumor behavior. Detection of DNA methylation in serum may be a biomarker for early detection of gastric cancer.

Aim: To detect tumor-associated DNA changes in stool samples among Iranian patients with colorectal cancer (CRC) compared to healthy individuals using BAT-26, p16 hypermethylation and long DNA markers., Methods: Stool DNA was isolated from 45 subjects including 25 CRC patients and 20 healthy individuals using a new, fast and easy extraction method. Long DNA associated with tumor was detected using polymerase chain reaction method. Microsatellite studies were performed utilizing denaturating polyacrylamide gel to determine the instability of BAT-26. Methylation status of p16 promoter was analyzed using methylation-specific PCR (MSP)., Results: The results showed a significant difference in existence of long DNA (16 in patients vs 1 in controls, P < 0.001) and p16 (5 in patients vs none in controls, P = 0.043) in the stool samples of two groups. Long DNA was detected in 64% of CRC patients; whereas just one of the healthy individuals was positive for Long DNA. p16 methylation was found in 20% of patients and in none of healthy individuals. Instability of BAT-26 was not detected in any of stool samples., Conclusion: We could detect colorectal cancer related genetic alterations by analyzing stool DNA with a sensitivity of 64% and 20% and a specificity of 95% and 100% for Long DNA and p16 respectively. A non-invasive molecular stool-based DNA testing can provide a screening strategy in high-risk individuals. However, additional testing on more samples is necessary from Iranian subjects to determine the exact specificity and sensitivity of these markers.