Publications by authors named "Masoud Sotoudeh"

100 Publications

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2020 Sep 10. Epub 2020 Sep 10.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.

Methods And Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.

Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
September 2020

Corrigendum to: Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK Biobank data.

Int J Epidemiol 2020 Dec 27. Epub 2020 Dec 27.

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1093/ije/dyaa268DOI Listing
December 2020

Association Between Serological Responses to Two Zoonotic Ruminant Pathogens and Esophageal Squamous Cell Carcinoma.

Vector Borne Zoonotic Dis 2021 Feb 29;21(2):125-127. Epub 2020 Oct 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Questionnaire data have linked contact with ruminants to the risk of esophageal squamous cell carcinoma (ESCC) in high-risk Asian populations. To better understand this observed association, we investigated exposure to two major zoonotic ruminant pathogens relative to ESCC risk. Using enzyme-linked immunosorbent assay, immunofluorescence assay, and microagglutination test assays, we measured immunoglobulin G anti- and anti- spp. antibodies in patients with ESCC ( = 177) and population-based controls ( = 177) matched by age, gender, and residence area from the Golestan case-control study in Iran. We found a similarly high seroprevalence of in ESCC cases and controls (75% and 80%, respectively), and a similarly low seroprevalence of spp. (0% and 0.6%, respectively). While documenting a high exposure to one of two zoonotic ruminant infections, this exposure failed to explain the observed association of ruminant contact and ESCC risk in this high-risk population.
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http://dx.doi.org/10.1089/vbz.2020.2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876355PMC
February 2021

Prognostic and Therapeutic Significance of Androgen Receptor in Patients with Gastric Cancer.

Onco Targets Ther 2020 2;13:9821-9837. Epub 2020 Oct 2.

Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: The clinical studies carried out in the last few decades unequivocally introduced activated androgen receptor (AR) as a pathogenic feature of human malignancies which not only endows cancer cells with survival advantage, but also may be exploited for anticancer interventions.

Patients And Methods: In this study, we have investigated the expression profile of and EMT-related genes in fresh gastric cancer (GC), adjacent nontumor and normal gastric tissues, as well as the effect and molecular mechanisms of inhibition in GC cell lines.

Results: Amongst 60 GC patients, 66.7% overexpressed that was remarkably correlated with the overexpression of . overexpression was also remarkably associated with unfavorable outcome (HR=3.478, =0.001); however, multivariate Cox regression analysis indicated that it was not an independent prognostic factor (HR=2.089, =0.056). This study has investigated simultaneous assessment of and EMT-related genes expression and indicated that concurrent overexpression of and is an independent unfavorable factor for GC overall survival after adjustment with other variables (HR=2.382, =0.021). Interestingly, the inhibition of signaling by potent antagonist enzalutamide suppressed cell growth, migration and invasion of GC cells via regulation of apoptosis-, cell cycle-, and EMT-related gene expressions.

Conclusion: Our findings have clinical importance proposing as an important prognostic factor involved in GC progression and metastasis, and submit inhibition as an appealing therapeutic approach for GC patients, either as a single agent or in a combined-modal strategy.
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http://dx.doi.org/10.2147/OTT.S265364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537849PMC
October 2020

Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study.

Nutr J 2020 09 28;19(1):108. Epub 2020 Sep 28.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country.

Methods: A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models.

Results: During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73-0.89), 0.83(0.76-0.92), 0.88(0.80-0.96) and 0.83(0.77-0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73-1.00) and 0.85(0.72-1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68-0.98)].

Conclusion: The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.
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http://dx.doi.org/10.1186/s12937-020-00627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523365PMC
September 2020

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Cancer Epidemiol Biomarkers Prev 2020 Dec 18;29(12):2642-2650. Epub 2020 Sep 18.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.

Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.

Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia ( < 0.004).

Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.

Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710574PMC
December 2020

Joint effect of diabetes and opiate use on all-cause and cause-specific mortality: the Golestan cohort study.

Int J Epidemiol 2020 Aug 18. Epub 2020 Aug 18.

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.

Methods: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.

Results: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.

Conclusions: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.
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http://dx.doi.org/10.1093/ije/dyaa126DOI Listing
August 2020

Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study.

Environ Health Perspect 2020 06 17;128(6):67002. Epub 2020 Jun 17.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers.

Objectives: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers.

Methods: During the period 2004-2008, a total of 50,045 Iranian individuals 40-75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with loss.

Results: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference , 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26).

Discussion: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907.
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http://dx.doi.org/10.1289/EHP5907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299082PMC
June 2020

Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study.

Lancet Glob Health 2020 05;8(5):e649-e660

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Evidence is emerging for a role of opiates in various cancers. In this study, we aimed to investigate the association between regular opium use and cancer incidence.

Methods: This study was done in a population-based cohort of 50 045 individuals aged 40-75 years from northeast Iran. Data on participant demographics, diet, lifestyle, opium use, and different exposures were collected upon enrolment using validated questionnaires. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between opium use and different cancer types.

Findings: During a median 10 years of follow-up, 1833 participants were diagnosed with cancer. Use of opium was associated with an increased risk of developing all cancers combined (HR 1·40, 95% CI 1·24-1·58), gastrointestinal cancers (1·31, 1·11-1·55), and respiratory cancers (2·28, 1·58-3·30) in a dose-dependent manner (p<0·001). For site-specific cancers, use of opium was associated with an increased risk of developing oesophageal (1·38, 1·06-1·80), gastric (1·36, 1·03-1·79), lung (2·21, 1·44-3·39), bladder (2·86, 1·47-5·55), and laryngeal (2·53, 1·21-5·29) cancers in a dose-dependent manner (p<0·05). Only high-dose opium use was associated with pancreatic cancer (2·66, 1·23-5·74). Ingestion of opium (but not smoking opium) was associated with brain (2·15, 1·00-4·63) and liver (2·46, 1·23-4·95) cancers in a dose-dependent manner (p<0·01). We observed consistent associations among ever and never tobacco users, men and women, and individuals with lower and higher socioeconomic status.

Interpretation: Opium users have a significantly higher risk of developing cancers in different organs of the respiratory, digestive, and urinary systems and the CNS. The results of this analysis show that regular use of opiates might increase the risk of a range of cancer types.

Funding: World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, US National Cancer Institute, International Agency for Research on Cancer.
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http://dx.doi.org/10.1016/S2214-109X(20)30059-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196888PMC
May 2020

Investigation of the Correlation between Androgen Receptor and ZEB1 and its Value in Progression of Gastric Cancer.

Avicenna J Med Biotechnol 2020 Jan-Mar;12(1):52-60

Hematology, Oncology and Stem Cell Transplantation Research Institute, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription factor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). It is well-known that ZEB1 mRNA expression is directly induced by both Estrogen Receptor (ER) and Progesterone Receptor (PR). Moreover, Androgen Receptor (AR) and PR could bind to the same regulatory element. Since it has been shown that AR overexpresses in Gastric Cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate whether AR could regulate ZEB1 expression in GC.

Methods: The expression profile of ZEB1 in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimens was assessed by qRT-PCR, and the association of ZEB1 expression with clinicopathological features was investigated. Furthermore, possible correlation between ZEB1 and AR was evaluated to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Finally, molecular interaction of ZEB1 and AR was assessed using a potent AR antagonist in GC cells.

Results: Among GC patients, 70.2% (40/57) overexpressed ZEB1 and 64.91% (37/57) overexpressed AR relative to normal gastric tissues. ZEB1 overexpression was significantly correlated with the AR overexpression in GC patients. Moreover, ZEB1 overexpression was remarkably associated with lower overall survival; however, it was not an independent prognostic factor. Evidence shows that simultaneous evaluation of ZEB1 and AR expression could independently predict survival of GC patients (HR= 2.193, p=0.047).

Conclusion: These findings have clinical importance suggesting simultaneous evaluation of ZEB1 and AR expression as a potential prognostic marker. Moreover, AR may regulate ZEB1 expression in GC cells proposing a possible promising targeted therapy for GC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035462PMC
March 2020

Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study.

EBioMedicine 2020 Mar 17;53:102643. Epub 2020 Feb 17.

International Agency for Research on Cancer (IARC), Lyon, France. Electronic address:

Background: Detecting pre-clinical bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. Telomerase reverse transcriptase (TERT) promoter mutations detectable in urine have emerged as promising BC biomarkers.

Methods: We performed a nested case-control study within the population-based prospective Golestan Cohort Study (50,045 participants, followed up to 14 years) and assessed TERT promoter mutations in baseline urine samples from 38 asymptomatic individuals who subsequently developed primary BC and 152 matched controls using a Next-Generation Sequencing-based single-plex assay (UroMuTERT) and droplet digital PCR assays.

Findings: Results were obtained for 30 cases and 101 controls. TERT promoter mutations were detected in 14 pre-clinical cases (sensitivity 46·67%) and none of the controls (specificity 100·00%). At an estimated BC cumulative incidence of 0·09% in the cohort, the positive and negative predictive values were 100·00% and 99·95% respectively. The mutant allelic fractions decreased with the time interval from urine collection until BC diagnosis (p = 0·033) but the mutations were detectable up to 10 years prior to clinical diagnosis.

Interpretation: Our results provide the first evidence from a population-based prospective cohort study of the potential of urinary TERT promoter mutations as promising non-invasive biomarkers for early detection of BC. Further studies should validate this finding and assess their clinical utility in other longitudinal cohorts.

Funding: French Cancer League, World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, the International Agency for Research on Cancer, and the U.S. National Cancer Institute.
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http://dx.doi.org/10.1016/j.ebiom.2020.102643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118568PMC
March 2020

Evaluation of the Association between Androgen Receptor and AURKA and Its Prognostic Value in Gastric Cancer.

Int J Hematol Oncol Stem Cell Res 2019 Oct;13(4):174-182

Hematology, Oncology and Stem Cell Transplantation Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

It is well-known that Aurora kinase A (AURKA) shows oncogenic properties in various tumor types including gastric cancer (GC). Moreover, previous studies have demonstrated that AURKA has a specific androgen receptor (AR) binding site in its promoter; thus, it could be regulated by AR. Since it has been shown that AR overexpresses in gastric cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate the association between AR and AURKA and its prognostic value in GC patients. : We assessed the expression profile of AURKA in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimen by qRT-PCR, and investigated the association of AURKA expression with clinicopathological features. Furthermore, we evaluated possible correlation between AURKA and AR to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Among GC patients, 65% (39/60) overexpressed AURKA relative to normal gastric tissues. AURKA overexpression was significantly correlated with the AR overexpression in GC patients. Although AURKA expression alone was not remarkably associated with poor outcome, we provided some evidence that combined evaluation of AURKA and AR expression could independently predict survival of GC patients adjusted for other variables (HR=1.7, CI=1.314-3.833 p=0.042). These results indicate that AR and AURKA may crosstalk to promote GC progression. Our findings have clinical importance because they suggest simultaneous assessment of AURKA and AR expression as a novel potential prognostic marker.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925368PMC
October 2019

The Correlation between EGFR and Androgen Receptor Pathways: A Novel Potential Prognostic Marker in Gastric Cancer.

Anticancer Agents Med Chem 2019 ;19(17):2097-2107

Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Despite worthy biologic rationale and numerous studies introducing therapeutic strategies targeting Epidermal Growth Factor Receptor (EGFR), phase III clinical trials have claimed that these current anti-EGFR agents did not significantly improve overall survival of Gastric Cancer (GC) patients. Therefore, to discover flawless candidates of anti-EGFR therapy and ideal prognostic markers, innovative studies are warranted.

Methods: The aim of this study was to assess the expression profile of EGFR in GC, adjacent non-tumor and normal gastric tissues by qRT-PCR, investigating the association of EGFR expression with clinicopathological features, evaluating possible molecular interaction between EGFR and Androgen Receptor (AR), and elucidating novel prognostic marker using Cox regression model.

Results: Among 60 GC patients, 70% (42/60) overexpressed EGFR relative to normal gastric tissues. EGFR overexpression was significantly correlated with the AR overexpression in GC patients. Although EGFR overexpression was remarkably associated with unfavorable outcomes (HR= 4.067, 95% CI= 1.228-13.467, p= 0.022), it was not an independent prognostic factor adjusted for other variables. However, we provided evidences that simultaneous evaluation of EGFR and AR expression, could independently predict the outcome of GC patients and could use as a precise prognostic marker. Moreover, it was revealed that induction or inhibition of AR signaling could alter the mRNA expression of EGFR in GC cell lines.

Conclusion: By targeting AR and EGFR using a potent AR inhibitor such as Enzalutamide, we postulate the possible crosstalk between EGFR and AR pathways in GC. Moreover, our study provided evidences elucidating a novel promising marker, simultaneous evaluation of EGFR and AR expression, which could properly predict prognosis of gastric cancer patients.
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http://dx.doi.org/10.2174/1871520619666190930142820DOI Listing
August 2020

ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy.

Cancer Immunol Immunother 2019 Oct 14;68(10):1597-1603. Epub 2019 Sep 14.

Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital, P.O. Box 14117-13135, Tehran, Iran.

Background: Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated.

Methods: Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient's history of neoadjuvant chemotherapy and/or radiotherapy, and the patient's overall survival.

Results: ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival.

Conclusions: Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.
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http://dx.doi.org/10.1007/s00262-019-02392-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493837PMC
October 2019

Pancreatic hydatid cyst diagnosed on EUS-guided FNA.

VideoGIE 2019 Aug 30;4(8):379-380. Epub 2018 Nov 30.

Division of Gastroenterology, Section of Interventional Endoscopy, Indiana University School of Medicine, Indianapolis, Indiana, USA.

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http://dx.doi.org/10.1016/j.vgie.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669307PMC
August 2019

Comparing Anthropometric Indicators of Visceral and General Adiposity as Determinants of Overall and Cardiovascular Mortality.

Arch Iran Med 2019 06 1;22(6):301-309. Epub 2019 Jun 1.

Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: It is unclear which anthropometric obesity indicator best predicts adverse health outcomes. This study aimed to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), and hip-adjusted WC with all-cause and cardiovascular mortality.

Methods: 50045 people aged 40-75 (58% women, median BMI: 26.3 kg /m2 ) participated in the population-based Golestan Cohort Study. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the association of obesity indicators with mortality. We also examined the association of these indicators with intermediate outcomes, including hypertension, blood glucose, dyslipidemia, carotid atherosclerosis, nonalcoholic fatty liver, and visceral abdominal fat.

Results: After a median follow-up of 10.9 years (success rate: 99.1%), 6651 deaths (2778 cardiovascular) occurred. Comparing 5th to the 1st quintile, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.12 (1.02-1.22) and 1.59 (1.39-1.83) for BMI, 1.16 (1.07-1.27) and 1.66 (1.44-1.90) for WC, 1.28 (1.17-1.40) and 1.88 (1.63-2.18) for WHtR, 1.44 (1.32-1.58) and 2.04 (1.76-2.36) for WHR, and 1.84 (1.62-2.09) and 2.72 (2.23-3.32) for hip-adjusted WC, respectively. Hip-adjusted WC had the strongest associations with the intermediate outcomes.

Conclusion: Indicators of visceral adiposity (e.g., hip-adjusted WC) were much stronger predictors of overall and cardiovascular mortality than were indicators of general adiposity (e.g., BMI). The full-strength effect of visceral adiposity becomes apparent only when both WC, as a risk factor, and hip circumference, as a protective factor, are individually and simultaneously taken into consideration.
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June 2019

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of total and cause-specific mortality: results from the Golestan Cohort Study.

Int J Epidemiol 2019 12;48(6):1824-1838

Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: To evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS).

Methods: A total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause.

Results: During 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers.

Conclusions: Our findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.
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http://dx.doi.org/10.1093/ije/dyz079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929526PMC
December 2019

Intravesical electromotive administration of botulinum toxin type A in improving the bladder and bowel functions: Evidence for novel mechanism of action.

J Spinal Cord Med 2021 Jan 18;44(1):89-95. Epub 2019 Apr 18.

Department of pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

To examine the hypothesis that what is the concomitant mechanism of action botulinum toxin type A (BoNTA) administration by intravesical electromotive into the bladder resulting in bladder function improvement. We also tried to confirm the possibility of retrograde trans-axonal transportation of toxin. Animal study. Ten male rabbits were divided into two groups. Group 1 (G1) ( = 5) (BoNTA/EMDA), and group 2 (G2) ( = 5) the control group. Animals in G1received 10 IU/Kg of intravesical BoNTA through a specific catheter for electromotive drug administration (BoNTA/EMDA). About 0.1-0.15 ml of toxin was diluted in 1 ml of distilled water. The maximum frequency of the device for drug solution delivery was set at 4 mA for 15 min. In G2 as the control group, the same procedure was performed to deliver normal saline to the bladder. Multiple biopsies were taken from bladder's contiguous structures one month postoperatively. The immunohistochemical (IHC) evaluation was performed with anti-clostridium botulinum toxoid type A mouse IgM monoclonal antibody. In specimens of G1, BoNTA penetrated through muscular layers of the bladder wall and the staining was uniform in the urothelium, interstitium, and muscular layers. Positive IHC staining showed that BoNTA was traced in the upper and lower spinal cord in addition to pelvic nerve, sacral nerve plexus, intestine wall, and pelvic floor muscle. In G2, all the specimens were intact in IHC staining. The presence of BoNTA in lower and upper spinal cord suggests the possibility of retrograde trans-axonal transfer of toxin to lower and upper neural pathways which may result in simultaneous improvement in bladder and bowel functions.
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http://dx.doi.org/10.1080/10790268.2019.1603490DOI Listing
January 2021

A prospective study of tea drinking temperature and risk of esophageal squamous cell carcinoma.

Int J Cancer 2020 01 20;146(1):18-25. Epub 2019 Mar 20.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Previous studies have reported an association between hot tea drinking and risk of esophageal cancer, but no study has examined this association using prospectively and objectively measured tea drinking temperature. We examined the association of tea drinking temperature, measured both objectively and subjectively at study baseline, with future risk of esophageal squamous cell carcinoma (ESCC) in a prospective study. We measured tea drinking temperature using validated methods and collected data on several other tea drinking habits and potential confounders of interest at baseline in the Golestan Cohort Study, a population-based prospective study of 50,045 individuals aged 40-75 years, established in 2004-2008 in northeastern Iran. Study participants were followed-up for a median duration of 10.1 years (505,865 person-years). During 2004-2017, 317 new cases of ESCC were identified. The objectively measured tea temperature (HR 1.41, 95% CI 1.10-1.81; for ≥60°C vs. <60°C), reported preference for very hot tea drinking (HR 2.41, 95% CI 1.27-4.56; for "very hot" vs. "cold/lukewarm"), and reported shorter time from pouring tea to drinking (HR 1.51, 95% CI 1.01-2.26; for <2 vs. ≥6 min) were all associated with ESCC risk. In analysis of the combined effects of measured temperature and amount, compared to those who drank less than 700 ml of tea/day at <60°C, drinking 700 mL/day or more at a higher-temperature (≥60°C) was consistently associated with an about 90% increase in ESCC risk. Our results substantially strengthen the existing evidence supporting an association between hot beverage drinking and ESCC.
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http://dx.doi.org/10.1002/ijc.32220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477845PMC
January 2020

MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma.

J Cell Biochem 2019 04 27;120(4):5010-5017. Epub 2018 Sep 27.

Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Gastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody-based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody-based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on-target and off-tumor toxicities owing to their higher sensitivity to low-level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off-tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.
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http://dx.doi.org/10.1002/jcb.27776DOI Listing
April 2019

Causes of premature death and their associated risk factors in the Golestan Cohort Study, Iran.

BMJ Open 2018 07 18;8(7):e021479. Epub 2018 Jul 18.

Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: To examine the causes of premature mortality (<70 years) and associated risk factors in the Golestan Cohort Study.

Design: Prospective.

Setting: The Golestan Cohort Study in northeastern Iran.

Participants: 50 045 people aged 40 or more participated in this population-based study from baseline (2004-2008) to August 2017, with over 99% success follow-up rate.

Main Outcome Measures: The top causes of premature death, HR and their 95% CI and population attributable fraction (PAF) for risk factors.

Results: After 444 168 person-years of follow-up (median of 10 years), 6347 deaths were reported, of which 4018 (63.3%) occurred prematurely. Ischaemic heart disease (IHD) accounted for 33.9% of premature death, followed by stroke (14.0%), road injuries (4.7%), stomach cancer (4.6%) and oesophageal cancer (4.6%). Significant risk/protective factors were: wealth score (HR for highest vs lowest quintile: 0.57, PAF for lowest four quintiles vs top quintile: 28%), physical activity (highest vs lowest tertile: 0.67, lowest two tertiles vs top tertile: 22%), hypertension (1.50, 19%), opium use (1.69, 14%), education (middle school or higher vs illiterate: 0.84, illiterate or primary vs middle school or higher: 13%), tobacco use (1.38, 11%), diabetes (2.39, 8%) and vegetable/fruit consumption (highest vs lowest tertile: 0.87, lowest two tertiles vs top tertile: 8%). Collectively, these factors accounted for 76% of PAF in men and 69% in women.

Conclusion: IHD and stroke are the leading causes of premature mortality in the Golestan Cohort Study. Enhancing socioeconomic status and physical activity, reducing opium and tobacco use, increasing vegetable/fruit consumption and controlling hypertension and diabetes are recommended to reduce premature deaths.
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http://dx.doi.org/10.1136/bmjopen-2018-021479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059279PMC
July 2018

Liver fibrosis alleviation after co-transplantation of hematopoietic stem cells with mesenchymal stem cells in patients with thalassemia major.

Ann Hematol 2018 Feb 17;97(2):327-334. Epub 2017 Nov 17.

Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Kargar Shomali Ave, Shariati Hospital, Tehran, Iran.

The aims of this study are to determine the replacement rate of damaged hepatocytes by donor-derived cells in sex-mismatched recipient patients with thalassemia major and to determine whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells (HSCs) can alleviate liver fibrosis. Ten sex-mismatched donor-recipient pairs who received co-transplantation of HSCs with mesenchymal stem cells were included in our study. Liver biopsy was performed before transplantation. Two other liver biopsies were performed between 2 and 5 years after transplantation. The specimens were studied for the presence of donor-derived epithelial cells or hepatocytes using fluorescence in situ hybridization by X- and Y-centromeric probes and immunohistochemical staining for pancytokeratin, CD45, and a hepatocyte-specific antigen. All sex-mismatched tissue samples demonstrated donor-derived hepatocyte independent of donor gender. XY-positive epithelial cells or hepatocytes accounted for 11 to 25% of the cells in histologic sections of female recipients in the first follow-up. It rose to 47-95% in the second follow-up. Although not statistically significant, four out of ten patients showed signs of improvement in liver fibrosis. Our results showed that co-transplantation of HSC with mesenchymal stem cells increases the rate of replacement of recipient hepatocytes by donor-derived cells and may improve liver fibrosis.
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http://dx.doi.org/10.1007/s00277-017-3181-9DOI Listing
February 2018

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

Gut 2017 12 11;66(12):2080-2086. Epub 2017 Sep 11.

Department of Pathology, Brigham & Women's Hospital, Boston, USA.

Objectives: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens.

Design: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected.

Results: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion.

Conclusion: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.
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http://dx.doi.org/10.1136/gutjnl-2017-314297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749338PMC
December 2017

Pancreatic Cancer is Associated with Peripheral Leukocyte Oxidative DNA Damage

Asian Pac J Cancer Prev 2017 05 1;18(5):1349-1355. Epub 2017 May 1.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Email:

Background: DNA damage accumulation has been linked to the cancer phenotype. The purpose of this study was to compare the levels of DNA base 8-hydroxy-2′-deoxyguanosine (8-OHdG) and C-reactive protein (CRP) inflammatory markers in healthy controls and pancreatic cancer patients from a hospital-based case-control study. Materials and Methods: Fifty-five pancreatic cancer patients and 55 healthy controls were enrolled from a pool of patients referred to the Endoscopic Ultrasound (EUS) center. Analysis of DNA content of peripheral blood cells was conducted for 8-OHdG with the 32P-postlabelling assay. Serum CRP levels were measured by high-sensitivity assays and demographic data for comparison were collected from individual medical records. Results: The group of cases showed significant increased median (IQR) 8-OHdG DNA adducts/106 nucleotides and CRP compared to the controls (208.8 (138.0-340.8) vs 121.8 (57.7-194.8) RAL value; P<0.001) and (3.5 (1.5-8.6) vs 0.5 (0.2-1.5) mg/L P<0.001). A number of conditional regression models confirmed associations of pancreatic cancer with oxidative DNA damage in peripheral leukocytes.Conclusions: Our findings suggest the importance of leukocyte 8-OHdG adducts as an indicator for systemic oxidative DNA damage in pancreatic cancer patients. In addition to increase in the CRP inflammatory marker, this supports the impact of inflammation in the occurrence of pancreatic cancer as well as inflammatory responses during cancer development.
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http://dx.doi.org/10.22034/APJCP.2017.18.5.1349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555546PMC
May 2017

MR enterography in nonresponsive adult celiac disease: Correlation with endoscopic, pathologic, serologic, and genetic features.

J Magn Reson Imaging 2017 10 9;46(4):1096-1106. Epub 2017 Feb 9.

Autoimmune and Motility Disorders of the Gastro-Intestinal Tract Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: To assess small bowel abnormalities on magnetic resonance enterography (MRE) in adult patients with nonresponsive celiac disease (CD) and investigate their associations with endoscopic, histopathologic, serologic, and genetic features.

Materials And Methods: This prospective study was carried out between September 2012 and August 2013. After approval by the Ethics Committee of our institution, informed consent was acquired from all participants. Forty consecutive patients with nonresponsive CD, aged 17-76 years, underwent MRE using a 1.5T unit. Sequences included T -HASTE, True-FISP, pre- and postcontrast VIBE to assess the quantitative (number of ileal and jejunal folds) and qualitative (fold pattern abnormalities, mural thickening, increased enhancement, bowel dilatation, or intussusception) measures. Endoscopic manifestations were categorized as normal/mild vs. severe. Histopathological results were divided into mild and severe. Genotyping of HLA-DQ2 and DQ8 was performed. Serum levels of tissue-transglutaminase, endomysial, and gliadin antibodies were also determined. Logistic regression analysis and receiver operating characteristic (ROC) curve were used.

Results: Twenty-nine (72.5%) cases showed abnormal MRE. Reversed jejunoileal fold pattern had significant association with severe endoscopic (odds ratio [OR] = 8.38, 95% confidence interval [CI] 1.73-40.5) and pathologic features (OR = 7.36, 95% CI 1.33-40.54). An increased number of ileal folds/inch was significantly associated with severe MARSH score and positive HLA-DQ8. (P < 0.001 and P = 0.026, respectively). Ileal fold number had the highest areas under the curve for prediction of severe endoscopic (AUC: 0.75, P = 0.009) and pathologic (AUC: 0.84, P < 0.001) findings and positive anti-transglutaminase antibody (AUC: 0.85, P = 0.027).

Conclusion: Fold pattern reversal on MRE is highly associated with endoscopic and pathologic features of refractory celiac disease (RCD). Increased ileal folds showed higher correlation with endoscopic-pathologic features, HLA-DQ8, and anti-transglutaminase level. MRE might be more sensitive for detection of increased ileal folds in CD rather than reduction of duodenal and jejunal folds due to better distension of ileal loops.

Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1096-1106.
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http://dx.doi.org/10.1002/jmri.25646DOI Listing
October 2017

Advanced colonic neoplasia in the first degree relatives of colon cancer patients: A colonoscopy-based study.

Int J Cancer 2016 11 10;139(10):2243-51. Epub 2016 Aug 10.

Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

We aimed to determine the risk of advanced neoplasms among a cohort of asymptomatic first degree relatives (FDRs) of patients with sporadic colorectal cancer (CRC) compared with matched controls. Data for patients with a diagnosis of CRC made between September 2013 and August 2014 were obtained from a population-based cancer registry system in Tehran. Screening colonoscopies were done for 342 FDRs and the findings were compared to those from 342 age- and gender-matched healthy controls without a family history of CRC. We reported the association as conditional Odds Ratio (OR) using Mantel Hazel and Logistic regression. The prevalence of advanced neoplasia was 13.2% among FDRs and 3.8% in controls (matched OR [mOR], 4.0, 95% confidence interval [CI], 2.1 - 7.6; p < 0.001). In FDRs aged 40-49 years, the prevalence of advanced neoplasia was significantly higher than in their matched controls (mOR, 6.8, 95% CI, 1.5-31.4; p = 0.01). Family history of CRC in at least one FDR was the strongest predictor of advanced neoplasia (adjusted OR, 4.0, 95% CI: 2.1-7.6; p < 0.001). The age of the index case at diagnosis did not predict the presence of advanced colonic neoplasms in their FDRs. Our study indicates a high risk of advanced neoplasia in FDRs of CRC cases, where only eight colonoscopies are needed to detect one advanced neoplasia. Our data suggest that all FDRs, regardless of the age of CRC diagnosis in their index case, should be considered for a targeted early screening.
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http://dx.doi.org/10.1002/ijc.30366DOI Listing
November 2016

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

Medicine (Baltimore) 2016 Jul;95(28):e3922

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences Gastrointestinal and Liver Disease Research Center, Firoozgar Hospital, Iran University of Medical Sciences Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Clinic, Tehran, Iran Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD American Cancer Society, Atlanta, GA Institute for Transitional Epidemiology and the Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.

Background And Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population.

Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39).

Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.
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http://dx.doi.org/10.1097/MD.0000000000003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956779PMC
July 2016

Driver Gene Mutations in Stools of Colorectal Carcinoma Patients Detected by Targeted Next-Generation Sequencing.

J Mol Diagn 2016 07 4;18(4):471-9. Epub 2016 May 4.

Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address:

Detection of driver gene mutations in stool DNA represents a promising noninvasive approach for screening colorectal cancer (CRC). Amplicon-based next-generation sequencing (NGS) is a good option to study mutations in many cancer genes simultaneously and from a low amount of DNA. Our aim was to assess the feasibility of identifying mutations in 22 cancer driver genes with Ion Torrent technology in stool DNA from a series of 65 CRC patients. The assay was successful in 80% of stool DNA samples. NGS results showed 83 mutations in cancer driver genes, 29 hotspot and 54 novel mutations. One to five genes were mutated in 75% of cases. TP53, KRAS, FBXW7, and SMAD4 were the top mutated genes, consistent with previous studies. Of samples with mutations, 54% presented concomitant mutations in different genes. Phosphatidylinositol 3-kinase/mitogen-activated protein kinase pathway genes were mutated in 70% of samples, with 58% having alterations in KRAS, NRAS, or BRAF. Because mutations in these genes can compromise the efficacy of epidermal growth factor receptor blockade in CRC patients, identifying mutations that confer resistance to some targeted treatments may be useful to guide therapeutic decisions. In conclusion, the data presented herein show that NGS procedures on stool DNA represent a promising tool to detect genetic mutations that could be used in the future for diagnosis, monitoring, or treating CRC.
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http://dx.doi.org/10.1016/j.jmoldx.2016.01.008DOI Listing
July 2016

Validation of Oxford Classification of Immunoglobulin A Nephropathy: an Iranian Experience.

Iran J Kidney Dis 2016 Jan;10(1):17-21

Department of Pathology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Introduction: In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists.

Materials And Methods: We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC).

Results: The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries.

Conclusions: The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future.
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January 2016

Mean Polyp per Patient Is an Accurate and Readily Obtainable Surrogate for Adenoma Detection Rate: Results from an Opportunistic Screening Colonoscopy Program.

Middle East J Dig Dis 2015 Oct;7(4):214-9

Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran ; Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Clinic, Tehran, Iran.

BACKGROUND The incidence of colorectal cancer is rising in several developing countries. In the absence of integrated endoscopy and pathology databases, adenoma detection rate (ADR), as a validated quality indicator of screening colonoscopy, is generally difficult to obtain in practice. We aimed to measure the correlation of polyp-related indicators with ADR in order to identify the most accurate surrogate(s) of ADR in routine practice. METHODS We retrospectively reviewed the endoscopic and histopathological findings of patients who underwent colonoscopy at a tertiary gastrointestinal clinic. The overall ADR and advanced-ADR were calculated using patient-level data. The Pearson's correlation coefficient (r) was applied to measure the strength of the correlation between the quality metrics obtained by endoscopists. RESULTS A total of 713 asymptomatic adults aged 50 and older who underwent their first-time screening colonoscopy were included in this study. The ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed good correlations between polyp detection rate (PDR) and ADR (r=0.93), and mean number of polyp per patient (MPP) and ADR (r=0.88) throughout the colon. There was a positive, yet insignificant correlation between advanced ADRs and non-advanced ADRs (r=0.42, p=0.35). CONCLUSION MPP is strongly correlated with ADR, and can be considered as a reliable and readily obtainable proxy for ADR in opportunistic screening colonoscopy programs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655841PMC
October 2015