Review Article

Systematic review of pancreatic cancer epidemiology in Asia-Pacific Region: major patterns in GLOBACON 2012

Mohamad Amin Pouhoseingholi, Sara Ashtari, Nastaran Hajizadeh, Zynab Fazeli, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 245-257

Pancreatic cancer is one of the deadliest cancers with short-term survival rates. Trends for pancreatic cancer incidence and mortality varied considerably in the world. To date, the causes of pancreatic cancer are not known sufficiently, although certain risk factors have been identified such as, smoking, obesity, life style, diabetes mellitus, alcohol, dietary factors and chronic pancreatitis. Since there are no current screening recommendations for pancreatic cancer, primary prevention is very important.  Therefore, up-to-date statistics on pancreatic cancer occurrence and outcome are essential for the primary prevention of this disease. Due to the lack of information on epidemiology of pancreatic cancer in most Asian countries, and limited of statistics and registration system in this area, we conducted a systematic review study to evaluate the most recent data concerning epidemiology of pancreatic cancer in Asia-Pacific region. In this review we focused on collected recent data on incidence, mortality, survival and risk factors of pancreatic cancer in this region. In addition, we reviewed and used the data of GLOBOCAN 2012 in this paper to complete the information as a source of compiling pancreatic cancer incidence and mortality rate.

Keywords: Pancreatic cancer, Epidemiology, Risk factors, Asia, Pacific.

Original Article

Economic burden made celiac disease an expensive and challenging condition for Iranian patients

Mohamad Amin Pourhoseingholi, Mohammad Rostami-Nejad, Farnoush Barzegar, Kamran Rostami, Umberto Volta, Amir Sadeghi, Zahra Honarkar, Niloofar Salehi, Hamid Asadzade-Aghdaei, Ahmad Reza Baghestani, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 258-262

Aim: The aim of this study was to estimate the economic burden of celiac disease (CD) in Iran.

Background: The assessment of burden of CD has become an important primary or secondary outcome measure in clinical and epidemiologic studies.

Methods: Information regarding medical costs and gluten free diet (GFD) costs were gathered using questionnaire and checklists offered to the selected patients with CD. The data included the direct medical cost (including Doctor Visit, hospitalization, clinical test examinations, endoscopies, etc.), GFD cost and loss productivity cost (as the indirect cost) for CD patient were estimated. The factors used for cost estimation included frequency of health resource utilization and gluten free diet basket. Purchasing Power Parity Dollar (PPP$) was used in order to make inter-country comparisons.

Results: Total of 213 celiac patients entered to this study. The mean (standard deviation) of total cost per patient per year was 3377 (1853) PPP$. This total cost including direct medical cost, GFD costs and loss productivity cost per patients per year.  Also the mean and standard deviation of medical cost and GFD cost were 195 (128) PPP$ and 932 (734) PPP$ respectively. The total costs of CD were significantly higher for male. Also GFD cost and total cost were higher for unmarried patients.

Conclusion: In conclusion, our estimation of CD economic burden is indicating that CD patients face substantial expense that might not be affordable for a good number of these patients. The estimated economic burden may put these patients at high risk for dietary neglect resulting in increasing the risk of long term complications.

Keywords: Celiac, Burden, Medical cost, Iran.

The Effect of Telenursing on Self-Efficacy in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

Sorur Javanmardifard, Fariba Ghodsbin, Mohammad Javad Kaviani, Iran Jahanbin

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 263-271

Aim: This study aimed to assess the effect of telenursing on nutritional behavior and physical activity self-efficacy in patients with non-alcoholic fatty liver disease (NAFLD).

Background: NAFLD is the most common liver disorder, which has a chronic course. Therefore, routine monitoring of these patients by medical staff helps them actively participate in the healing process and promote their self-efficacy.

Methods: In this randomized controlled clinical trial, 60 patients were chosen through convenience sampling among patients with NAFLD. After obtaining written informed consents, the participants were randomly divided into an intervention and a control group (each containing 30 subjects). The participants received diet consultation individually and were taught how to perform physical activities. Telephone intervention was conducted in the intervention group for 12 weeks. The study questionnaires were completed by the participants before and after the intervention. The data were analyzed using the SPSS statistical software.

Results: Based on the results, the mean score of nutritional behavior and physical activity self-efficacy increased in the study groups after the intervention. This increase was statistically significant only in the intervention group. Additionally, the two groups were significantly different regarding the mean scores of nutritional behavior and physical activity self-efficacy.

Conclusion: Telenursing could improve self-efficacy and physical activity in patients with NAFLD.

Keywords: Non-alcoholic fatty liver, Diet, Physical activity, Telenursing, Self-efficacy.

Analysis of TLR7, SOCS1 and ISG15 immune gene expressions in the peripheral blood of responder and non-responder patients with chronic Hepatitis C

Razieh Dowran, Jamal Sarvari, Afagh Moattari, Mohammad Reza Fattahi, Ramezani Amin, Seyed Younes Hosseini

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 272-277

Aim: To evaluate the baseline expression of the immune genes in PBMCs of responder and non-responder patients with chronic Hepatitis C.

Background: Although the contribution of peripheral blood mononuclear cell (PBMC) gene expression in treatment outcome of hepatitis C virus (HCV) infection is supposed, it has remained to be distinctly delineated. The baseline expression of the immune genes inside PBMCs may reflect the responsiveness status following IFN treatment.

Methods: Totally, 22 chronic HCV encompasses 10 responders and 12 non-responsive cases enrolled randomly regarding medical records. The PBMCs from the peripheral blood samples were isolated and then incubated for 6 hours in the culture media. The baseline expression of TLR7, SOCS1 and ISG15 was measured by Real time PCR.

Results: The gene expression pattern in PBMCs of both groups showed a similar trend. The expression of SOCS1 and TLR7 genes showed higher levels in non-responder group (P>0.05). The result of ISG15 showed a higher but non-significant expression in the responder group (P>0.05).

Conclusion: The similar pattern of TLR7, SOCS1 and ISG15 expression in the responder and non-responder patients indicated their poor discriminating and predictive value in PBMCs sample.

Keywords: Hepatitis C virus, ISG15, SOCS1, TLR7, Responder.

Results: The gene expression pattern in PBMCs of both groups showed a similar trend. The expression of SOCS1 and TLR7 genes showed higher levels in non-responder group (P>0.05). The result of ISG15 showed a higher but non-significant expression in the responder group (P>0.05).

Conclusion: The similar pattern of TLR7, SOCS1 and ISG15 expression in the responder and non-responder patients indicated their poor discriminating and predictive value in PBMCs sample.

The relationship between expression of Toll-like Receptor 4 in chronic hepatitis C patients and different stages of liver fibrosis

Salem Youssef Mohamed, Ehab Fawzy Mostafa, Amr Shaaban Hanafy, Hesham Atia, Ashraf Metwally, Ayman M. Marei

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 278-283

Aim: The objective of this work is to find out whether there is a relation between the expression of TLR4 and fibrosis progression in chronic HCV patients.

Background: Toll-like Receptor 4 (TLR4) is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines.

Methods: Fifty patients with chronic HCV were included. They were divided into group A: 40 patients (F1-F4) and group B (control group) which included ten patients (F0) based on fibroscan value. All patients were exposed to clinical and laboratory evaluations preliminary to antiviral therapy, assessment of TLR4 mRNA by Real Time- PCR.

Results: Twenty-eight males and 22 females with a mean age 28.9±6.1 years. The mean TLR4 expression is 11.2±7.4 folds, TLR4 expression in F0 group is 2.8±1.9, in F1 group 4.8±1.5, F2 group 10.2±2.5, F3 group 16.8±1.5 and in F4 21.3±3.6 folds (p<0.001). TLR4 showed a positive correlation with age, fibrosis stage, HCV RNA, serum transaminases, total bilirubin and prothrombin time, a negative correlation with platelet count and serum albumin. Fibrosis progression was independently associated with TLR4 expression (?=0. 648, P<0.0001), RNA (?= 0.160, P =0.001) and platelet count (?= -0.248, P = 0.004).

Conclusion: The expression of TLR4 is highly correlated with the fibrosis progression; TLR4 may be a potential target for drugs to limit the progression of fibrosis.

Keywords: Toll-like Receptor 4, Chronic HCV patients, Liver fibrosis, Fibroscan, HCV RNA.

Association of the epidermal growth factor gene +61A>G polymorphism with hepatocellular carcinoma in an Iranian population

Mehdi Gholizadeh, Ayyoob Khosravi, Pedram Torabian, Naghmeh Gholipoor, Nader Mansour Samaei

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 284-288

Aim: The aim of this study was to address the association of the EGF gene +61A/G polymorphisms and HCC susceptibility in an Iranian population.

Background: The association of epidermal growth factor (EGF) gene +61A/G polymorphism (rs4444903) and hepatocellular carcinoma (HCC) has been investigated in several populations. However, the findings are controversial.

Methods: A total of 40 unrelated HCC patients and 106 healthy individuals were enrolled in this study. Genomic DNA of HCC patients was extracted from formalin-fixed, paraffin-embedded samples using CinnaPure DNA kit according to manufacturer’s instructions. Genomic DNA of healthy individuals, also, was extracted from peripheral blood cells using the boiling method. The rs4444903 (A/G) polymorphism was genotyped using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method.

Results: Significant association was found for the EGF +61A allele and HCC risk [OR = 1.72, 95% CI (1.02 - 2.90), P value = 0.04]. Also, significant association was observed for the EGF +61A/G genotypes and HCC risk under codominant and dominant models by SNPStats software analysis.

Conclusion: Our findings suggest that the EGF gene +61A/G polymorphism (rs4444903) might be a risk factor for susceptibility to HCC in Iranian population. However, further studies using more samples are needed.

Keywords: Epidermal growth factor, EGF +61A>G polymorphism, Hepatocellular carcinoma.

Reliability and Validity of the Persian Version of Patient Assessment of Constipation: Quality of Life (PAC-QOL) Questionnaire

Marjan Mokhtare, Seyed-Mohammad-Sadegh Ghafoori, Mojtaba Soltani-Kermanshahi, Amir-Hosein Boghratian, Shahram Agah, Mehrdad Sheikhvatan

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 289-294

Aim: The present study aimed to assess the reliability and validity of Persian version of patient assessment of constipation: quality of life (PAC-QOL) questionnaire in Iranian patients.

Background: Chronic constipation has significant effects on daily living, wellbeing and individuals' quality of life (QOL). Validated tools can help us to assessing QOL in affected ones and facilitating clinical management of them.

Methods: The English version of Patient Assessment of Constipation: Quality of Life (PAC-QOL) was translated into the Persian language and was confirmed by back-translation. One hundred and forty patients with functional constipation, according Rome III criteria, completed the questionnaires .The questionnaires were analyzed using Cronbach's Alpha internal consistency score to determine the reliability. Twenty medical experts were then asked to evaluate the PAC-QOL and the results were used to calculate the Content Validity Ratio (CVR) and Content Validity Index (CVI).

Results: Due to obtained value for Cronbach`s ? (0.975) and also for the subscale of physical discomfort (0.930), psychosocial discomfort (0.975) and worries and concerns (0.915), the internal consistency is established. According to medical   experts’ opinions, the value of CVR ranged from 0.5 to 0.8 and the value of CVI was 0.81.

Conclusion: The Persian version of PAC-QOL questionnaire is shown to have acceptable reliability and validity to be used for psychometric evaluation in Iranian patients complaining of functional constipation.

Keywords: Quality of life, Reliability, Validity, Persian, Constipation.

Network analysis of common genes related to esophageal, gastric, and colon cancers

Padina Vaseghi Maghvan, Mostafa Rezaei –Tavirani, Hakimeh Zali, Abdolrahim Nikzamir, Saeed Abdi, Mahsa Khodadoostan, Hamid Asadzadeh-Aghdaei

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 295-302

Aim: The aim of this study was to provide a biomarker panel for esophageal, gastric and colorectal cancers. It can help introducing some diagnostic biomarkers for these diseases.

Background: Gastrointestinal cancers (GICs) including esophageal, gastric and colorectal cancers are the most common cancers in the world which are usually diagnosed in the final stages and due to heterogeneity of these diseases, the treatments usually are not successful. For this reason, many studies have been conducted to discover predictive biomarkers.

Methods: In the present study, 507 genes related to esophageal, gastric and colon cancers were extracted.. The network was constructed by Cytoscape software (version 3.4.0). Then a main component of the network was analyzed considering centrality parameters including degree, betweenness, closeness and stress. Three clusters of the protein network accompanied with their seed nodes were determined by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO) analysis of the key genes in combination to the seed nodes was performed.

Results: The network of 17 common differential expressed genes in three esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges were constructed. Eight crucial genes were determined. Three Clusters of the network were analyzed by GO analysis.

Conclusion: The analyses of common genes of the three cancers showed that there are some common crucial genes including TP53, EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to gastrointestinal cancers and can be predictive biomarkers for these cancers.

Keywords: Colon cancer, Gastric cancer, Esophageal cancer, Gene ontology, Biomarker.

Celiac disease and hepatitis C relationships in transcriptional regulatory networks

fereshteh izadi, Mostafa Rezaei Tavirani, Zahra Honarkar, Mohammad Rostami Nejad

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 303-310

Aim: we mainly aimed to elucidate potential comorbidities between celiac disease and hepatitis c by means of data and network analysis approaches.

Background: understanding the association among the disorders evidently has important impact on the diagnosis and therapeutic approaches. Celiac disease is the most challenging, common types of autoimmune disorders. On the other hand, hepatitis c virus genome products like some proteins are supposed to be resemble to gliadin types that in turn activates gluten intolerance in people with inclined to gluten susceptibilities. Moreover, a firm support of association between chronic hepatitis and celiac disease remains largely unclear. Henceforth exploring cross-talk among these diseases will apparently lead to the promising discoveries concerning important genes and regulators.

Methods: 321 and 1032 genes associated with celiac disease and hepatitis c retrieved from DisGeNET were subjected to build a gene regulatory network. Afterward a network-driven integrative analysis was performed to exploring prognosticates genes and related pathways.

Results: 105 common genes between these diseases included 11 transcription factors were identified as hallmark molecules where by further screening enriched in biological GO terms and pathways chiefly in immune systems and signaling pathways such as chemokines, cytokines and interleukins.

Conclusion: in silico data analysis approaches indicated that the identified selected combinations of genes covered a wide range of known functions triggering the inflammation implicated in these diseases.

Keywords: celiac disease, hepatitis c, regulatory network.

Cryptosporidium species subtypes and associated clinical manifestations in Indian patients

Shehla Khalil, Bijay Ranjan Mirdha, Ashutosh Panda, Yogita Singh, Jaishree Paul, Govind Makharia

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 311-318

Aim: Present hospital based study was carried out at our tertiary care centre with an aim to study the distribution of Cryptosporidium species subtypes in patients with complaints of diarrhea.

Background: Cryptosporidium species are one of the important causative agents of parasitic diarrhea, amongst which Cryptosporidium hominis (C.hominis) and Cryptosporidium parvum (C.parvum) are the two major species that are associated with human cryptosporidiosis.

Methods: Four hundred and fifty (n=450) diarrheic patients complaining of different types of diarrhea were enrolled in the present study. Both microscopic and molecular diagnostic methods were used for the detection as well as for identification of Cryptosporidium species and its speciation and subtyping.

Results: Forty one (n=41) and forty three (n=43) patients were positive for Cryptosporidium species by microscopy and Polymerase chain reaction (PCR) assay respectively. Of these 43 cases, 70% (30/43) were identified as C. hominis and 21% (9/43) was as C. parvum, 7% (3/43) was as Cryptosporidium felis (C.felis) and 2% (1/43)as Cryptopsoridium viatorum (C. viatorum) respectively . Upon subtyping of C. hominis and C. parvum, 16 subtypes belonging to 8 different subtype families could be identified.  The frequency of different families were Ia (13%, 5/39), Ib (15%, 6/39), Id (18%, 7/39), Ie (30%, 12/39) and IIa (5%, 2/39), IIc (8%, 3/39), IId (8%, 3/39) and IIe (3%, 1/39).

Conclusion: Our study results strongly suggest and reinforces the fact that most of the human cryptosporidiosis is anthroponotic and we expect that present molecular epidemiological data will provide more insight to unravel the changing clinical paradigm of human cryptosporidiosis at large.

Keywords: Cryptosporidium, Genetic variations, Glycoprotein gp60, phylogeny.

Brief Report

Molecular Characterization of Shigella spp. isolates from a pediatric hospital in Southwestern Iran

Leili Shokoohizadeh, Gholam Abbas Kaydani, Alireza Ekrami

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 319-322

Aim: In This study focused on the detection of dominant clones and genetic relationship of Shigella spp.  isolated   from children with diarrhea in the main pediatric hospital in Ahvaz by multi-locus sequence typing (MLST) technique.

Background: Shigellosis is considered as one of the problematic bacterial infections for public health in the world. Khuzestan province in the Southwestern part of Iran is a known endemic area for infections due to Shigella. There are limited molecular epidemiological data for Shigella spp. in this area.

Methods: A total of 50 Shigella spp. were isolated from January-June 2015 based on conventional microbiology and serology tests. The Sequence types (ST) of Shigella isolates which are characterized by Enterobacterial repetitive intergenic consensus (ERIC-PCR) were detected by MLST technique.

Results: Among 50 Shigella isolates, a total of 31(62%), 16(32%) and 3 (6%) of Shigella isolates were identified as S. flexneri, S.sonneii, and S.boydii, respectively. Two different sequence types (ST152 and ST245) were identified in Shigella isolates. ST152 was detected in S.sonnei and ST245 in S. flexneri and S. boydii isolates.

Conclusion: Based on MLST data, the stable and genetically linked Shigella clones are the cause of Shigella infections in children in Southwestern Iran.

Keywords: Shigella, Multi-Locus Sequence Typing, Iran.

Case Report

Development of PBC/SSc overlap syndrome in chronic GVHD patient: immunological implications in the presence of mitochondrial, nucleolar and spindle midzone autoantigens

Roberto Assandri, Federico Serana, Alessandro Montanelli

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 323-331

Chronic Graft versus Host Disease (cGVHD) is a complex disease resulting from donor T-cell recognition of a genetically disparate recipient that is unable to reject donor cells after allogeneic Stem Cell Transplantation (HSCT). cGVHD has some features resembling to autoimmune diseases (AD) such as Sjögren syndrome, primary biliary cirrhosis (PBC) and scleroderma (SSc). Also patients with cGVHD could develop extensive cGVHD with scleroderma-like skin manifestations and other clinical signs similar to those of patients with scleroderma. We take into consideration a patient with GVHD that developed PBC/SSc overlap syndrome with a complex and particular autoantibodies profile. Indirect immunofluorescence (IIF) with double coloration showed a cytoplasmic mitochondrial-like pattern, a clumpy nucleolar staining pattern, and a cell-cycle related staining pattern. Following anaphase onset, proteins regulator of cytokinesis localizes to the overlap zone on the ends of midzone microtubules and becomes compacted during furrow ingression to form the midbody. Second level tests confirmed the presence of anti-mitochondrial antibodies M2-subunit but no other autoantibodies were found. We performed a home-made immunoblot analysis that identified a 37 kDa fibrillarin band, and not identify 47 kDa, 31KDa and 18/20 kDa bands. After literature review of these possible cellular localizations, the proteins recognized by our patient’s serum seem likely to be Aab to core midzone organizer components. However, due to the unavailability of the proper techniques in our laboratory, we were not able to further characterize them.  The pathogenesis and morbidity of cGVHD after HSCT remains enigmatic, but the presence of specific autoantibodies are the hallmark of AD and represent a possibility of differential diagnosis. Standard techniques combined with the use of non-routinely laboratory techniques are a usefully and complementary method for studying difficult and particular cases. In fact, these autoantibodies will be considered as ‘‘diagnostic’’ and not as ‘‘esoteric’’ antibodies. In conclusion, a re-assessment of the diagnostic protocols in cGVHD together with a precise observation of the clinical and laboratory picture will ultimately help us clarify the disease and could provide a better understanding of the immune network deregulation.

Keywords: GVHD, Immunological implications, Treatment.

PAX-5 positive anaplastic large cell lymphoma presenting by dysphagia Case report

Negar Azarpira, Akbar Safaie, Ahmad Monabati, Masudd Hosseinzadeh, Sadat Noori, Maryam Moini, Alireza Rahimi, Tahereh Heidari, Marjan Rahsaz

Gastroenterology and Hepatology from Bed to Bench, Vol. 10 No. 4 (2017), 30 October 2017, Page 332-336

Anaplastic large cell lymphoma (ALCL) is a distinct pathologic entity with characteristic morphologic, im¬munophenotypic and cytogenetic features.  Obstructive symptoms are rare presentation of ALCL. We report a 16-year-old boy who initially presented with dysphagia. Upper gastrointestinal endoscopy revealed severe stenosis with an infiltrative process starting from 24 cm of incisors in lower esophagus Esophageal mucosal biopsy demonstrated lymphomatous involvement that ancillary tests confirmed the diagnosis of ALCL, ALK (kinase-positive), and PAX5 positive. The patient responded to CHOP-based chemotherapy. This case illustrated an unusual presentation of primary Non Hodgkin lymphoma of esophagus.

Keywords: PAX5, Anaplastic large cell lymphoma, Esophagus, stricture.

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