Systematic Review and Meta-Analysis

Prevalence of anal fistulas: A systematic review and meta-analysis

Arash Sarveazad, Mansour Bahardoust, Jebreil Shamseddin, Mahmoud Yousefifard

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Anal fistula refers to a clinical condition with local pain and inflammation associated with purulent discharge that affects the quality of life. Due to the lack of studies, the presence of bias, and high heterogeneity in the studies, a systematic review has been performed on the population-based database in this field for the first time in this study.The present systematic review and meta-analysis were performed according to MOOSE guidelines. After systematic searching in electronic databases, only four articles met the inclusion criteria. After preparing a checklist and extracting data from the relevant articles, a meta-analysis was performed.All studies on the prevalence of anal fistula are related to Europe, and so far, no study has been conducted in other continents.  The overall prevalence of anal fistula in European countries was 18.37 (95% CI: 18.20-18.55%) per 100,000 individuals and the highest prevalence reported for Italy [ 23.20 (95% CI: 22.82 to 23.59) per 100,000 people].From the present population-based (224,097,362) study results, it can be concluded that there is a large knowledge gap in this context. Because all the studies included in this study are only related to Europe, the need to study in this field is strongly felt in other countries.

Viral hepatitis is associated with an increased risk of severe outcome from coronavirus disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

Timotius Ivan Hariyanto, Claudia Jodhinata, Devina Adella Halim, Andree Kurniawan

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background: Coronavirus disease 2019 has been a worldwide concern that creates a major issue in many aspects.  It is important to identify severe outcomes’ risk factors. To date, viral hepatitis and severe COVID-19 association is not yet established.

Aims: The purpose of this study is to analyze the potential association between viral hepatitis and the severity of COVID-19.

Methods: Through August 5th, 2020 we systematically searched the PubMed and PubMed Central (PMC) using specific keywords related to our focus. All articles published on COVID-19 and viral hepatitis were retrieved. Using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 Software, the statistical analysis was done.

Results: Our analysis included a total of 16 studies with a total of 14,682 patients. Our meta-analysis showed that viral hepatitis increases the risk of developing severe COVID-19 [RR 1.68 (95% CI 1.26 – 2.22), p = 0.0003, I2 = 21%, random-effect modelling]. According to meta-regression analysis, the association between viral hepatitis and severe COVID-19 was not influenced by age (p = 0.067), diabetes (p = 0.057), and other liver disease (p = 0.646).

Conclusion: An increase of severe COVID-19 risk is associated with viral hepatitis. To reduce the risk of COVID-19, patients with viral hepatitis should be monitored carefully.

Original Article

Natural Adjuvants (PC and G2) Induce Activated Natural Killer Cells with NKG2D Expression and Cytotoxic Properties in Colorectal Cancer

Ali khodadadi, Abdulhasan Talaiezadeh, Yuji Heike Heike, Hamid Galehdari, Mojtaba Oraki Kohshour, Abdulkarim Sheikhi, Seyed Nematollah Jazayeri, Mohammad Pedram, Mehrdad Borhani, Ali Asadirad

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Colorectal cancer is one of the most commonly reported cancers. Cell and gene therapies of cancer have received much attention in the past decade. Natural killer (NK) cells are an element of the innate immune system that can recognize and kill cancer cells and provide hope for cancer therapy. One of the current methods in tumor immunotherapy is NK cell therapy. Here, it was proposed that PC and G2 adjuvants can function as NK activator to convert these cells into the cytotoxic natural killer cell for further cytotoxicity effect.

For this purpose, 12 Patients with colorectal cancer were qualified for this study. Peripheral blood mononuclear cell (PBMC) of each patient with two distinctive concentrations (  and 5    Cells/well) was treated with Interleukin2 (IL2), PC, and G2 adjuvant separately. The NK cell's surface marker, including CD16, CD56, and NKG2D, was evaluated by flow cytometry. The cytotoxicity of treated PBMCs as effector cells against NK sensitive cells line (K562) was evaluated with the LDH assay method.

The results showed that the PC and G2 adjuvants could induce cytotoxic NK cells with high expression of NKG2D. Besides, the PC and G2 adjuvants could induce cytotoxic natural killer cells with cytotoxicity against K562 cells.

Finally, it can be stated that the PC and G2 adjuvants could be a candidate to induce cytotoxic killer cell.

Evaluation of CD10 expression as a diagnostic marker for colorectal cancer

Jakub Żurawski, Patrycja Talarska, Mateusz de Mezer, Krzysztof Kaszkowiak, Michał Chalcarz, Katarzyna Iwanik, Jacek Karoń, Piotr Krokowicz

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background and aims

Adenocarcinoma is diagnosed in one out of 20 individuals in the USA and western-European countries. Its prognosis and treatment depend largely on the severity of the disease at the time of diagnosis. Additional new biological markers are being sought that can help diagnose colon cancer at an early stage. One such marker present in both serum and tumor tissue is CD10.



The concetration of CD10 were tested by ELISA and immunohistochemistry in the serum and tissue samples, respectively, from 113 patients, diagnosed histopathologically and treated for adenocarcinoma of the colon.

Additionally, ROC curve with optimal cut-off point based on Youden’s criterion was calculated for CD10.



Serum concetrations of CD10 and its tissue expression in patients diagnosed with adenocarcinoma of the colon correlate with cancer staging based on the Astler-Coller-Dukes classification.

In order to ascertain the optimal cut-off point for CD10 as a predictor of belonging to the study group, ROC curve was prepared for CD10. Optimal cut-off point for CD10 was 0.57, with prediction of belonging to the study group for CD10 ≥ 0.57.



CD10 could, therefore, be a useful marker in the early diagnosis of adenocarcinoma of the colon.

Evidence of Histone Modification Affecting the ARID1A Expression in Colorectal Cancer Cell lines

Mehran Erfani, Mozhdeh Zamani, Pooneh Mokarram

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Aim: This study aimed to focus on the role of histone deacetylation in reduced ARID1A expression in colorectal cancer cell lines.

Background: ARID1A, a subunit of the switch/sucrose nonfermentable chromatin remodeling complex, has emerged as a bona fide tumor suppressor and is frequently down regulated and inactivated in multiple human cancers. Epigenetic modifications have an important role in dysregulation of gene expression in cancer. DNA methylation has been reported as an important regulator of ARID1A expression in colorectal cancer cell lines, however, histone modification role in ARID1A suppression in colorectal cancer remains unclear. Methods: The expression levels of ARID1A mRNA were determined using real-time quantitative PCR in colorectal cancer cell lines including HCT116, SW48, HT29, SW742, LS180 and SW480. In order to evaluate the effect of histone deacetylation on ARID1A expression, all cell lines were treated by trichostatin A (TSA), a histone deacetylase inhibitor. SPSS software (Version 23) and GraphPad Prism (Version 6.01) were applied for data analysis using the one-way ANOVA, followed by Tukey’s multiple comparison tests. Results: Treatment of colorectal cancer cell lines with TSA increased ARID1A expression in a cell line-dependent manner, suggesting that histone deacetylation is at least one factor, contributing to ARID1A downregulation in colorectal cancer. Conclusion: Histone deacetylases inhibitors might provide a strategy to restore ARID1A expression, and may bring benefits to the colorectal cancer patients with a broader range of genetic backgrounds.

Effect of valproic acid on SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 genes expression and cell growth inhibition in colon carcinoma

Masumeh Sanaei , Fraidoon Kavoosi, Masoud Safarzadeh

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Backgrounds: Cancer is a process induced by the accumulation of epigenetic alterations such as DNA methylation and histone deacetylation. The DNA methylation and histone deacetylation of tumor suppressor genes (TSGs) have been shown in various cancers. Recent studies have shown that silencing of TSGs, resulting from epigenetic alterations such as deacetylation, is an early event in many human cancers. The methylation and deacetylation of suppressor of cytokine signaling (SOCS) family, as TSGs, have been demonstrated in numerous cancers. Histone deacetylase inhibitors (HDACIs) have emerged as the accessory therapeutic agents for human cancers, they can inhibit the activity of specific HDACs, restore the expression of some TSGs, and induce cell growth inhibition and apoptosis. The current study aimed to investigate the effect of valproic acid (VPA) on SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene expression and cell growth inhibition in colon carcinoma IS1, IS2, and IS3 cell lines. Materials and Methods: The IS1, IS2, and IS3 cells were cultured and treated with VPA. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. Results: VPA changed the expression level of the SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene by which induced cell apoptosis and inhibit cell growth in all three cell lines, IS1, IS2, and IS3. Conclusion: VPA can induce apoptosis through reactivation of SOCS-1, SOCS-2, SOCS-3, SOCS-5, SOCS6, and SOCS-7 gene expression.

Comparison of Fluoxetine and Duloxetine Hydrochloride therapeutic effects on Patients with constipation-predominant Irritable Bowel Syndrome

Sattar Jafari, Behnam Sajedi , Maryam Jameshorani , Fatemeh Salarpour

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background Irritable bowel syndrome with constipation (IBS-C) is a functional bowel disorder characterized by changes in bowel movements and abdominal pain in the absence of identifiable structural abnormalities. Despite much progress in the treatment of other types of IBS, limited treatments are available for IBS-C. Therefore, in this study, as a few randomized clinical trials have verified selective and norepinephrine reuptake inhibitors efficacy in IBS, an inclusive comparison was made between them, and their effectiveness was proven in IBS-C.


Materials and Methods: 182 IBS-C patients were selected and haphazardly divided into 3 groups according to the type of treatment: One group was given 20 mg of Dicyclomine and Fluoxetine, the second group received Dicyclomine along with Duloxetine Hydrochloride, and the third group received only Dicyclomine for two months. The severity of symptoms was recorded by a questionnaire at the beginning and the end of the treatment.


Results: The average age and BMI of the patients were 28.5 ± 5.2 years and 25.2 ± 2.4 kg/m2, respectively. Duloxetine was more effective than Fluoxetine in reducing flatulence (p=0.043), abdominal pain intensity (p≤0.046) and duration (p≤0.003) and increasing the quality of life (p≤0.046) and the frequency of fecal excretion in the patients (p≤0.004).

Conclusion: Based on the study findings, the therapeutic effects of Fluoxetine and Duloxetine on all symptoms of IBD were more than Dicyclomine and Duloxetine’s impacts, specifically, were more than Fluoxetine. Further studies in larger groups to find the best dosage and side effects of these drugs are suggested.

Keywords: Fluoxetine, Duloxetine Hydrochloride, Irritable bowel syndrome, constipation

Preoperative esophagogastroduodenoscopy findings and effects on laparoscopic Roux-en-Y gastric bypass in area with high prevalence of Helicobacter pylori infection: Multi-center experience in Iran

Mehdi Alimadadi , Seyedali Seyedmajidi, Sina Safamanesh, Elena Zanganeh , Seyed Ashkan Hosseini, Shahin Hajiebrahimi, Mohammadreza Seyyedmajidi

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background and study aim: Esophagogastroduodenoscopy (EGD) and Helicobacter pylori testing are routine parts of preoperative assessment of bariatric surgery at many centers. We aim to evaluate EGD and Helicobacter pylori status affect laparoscopic Roux-en-Y gastric bypass (RYGB) in area with high prevalence of Helicobacter pylori infection.

Patients and methods: This was a cross‑sectional study of all patients underwent EGD before laparoscopic RYGB in three gastroenterology centers in Iran between January 2018 and December 2020. All patients were diagnosed to be Helicobacter pylori status by histopathological examination.

Results: 637 patients (52.4% female) were enrolled in this study. 46.8% of patients had any abnormal mucosal appearance. In 0.6%, surgery was canceled (esophageal varices, gastric malignancies). 1.7% needed endoscopic intervention (gastric polyps and bezoars) and 11.9% needed medical management (severe esophagitis, peptic ulcer disease, erosive gastritis/ duodenitis). The prevalence of H. pylori was 61.5% and there was no statistical difference in the prevalence in groups of normal and abnormal EGD. 88.8% of patients with normal mucosal appearance in EGD were asymptomatic and 92.6% in group with abnormal EGD were symptomatic (p=0.01). Without considering H. pylori status, EGD could just influence in 13.7% surgery time and 0.6% surgery canceling.

Conclusion: Even with considering high H. pylori prevalence in Iran, using EGD as a routine investigation in the preoperative assessment for RYGB surgery would not have a significant impact. If clinically symptoms and/or signs are present, the patient should go through an appropriate evaluation with EGD.

Endoscopic, laboratory, and clinical findings and outcomes of caustic ingestion in adults; a retrospective study

Ali Banagozar-Mohammadi, Maryam Zaare-Nahandi, Ali Ostadi, Anahita Ghorbani, Shahin Hallaj

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background: With an incidence rate of 200,000 cases annually and the induction of numerous complications, caustic ingestion imposes a significant burden on the healthcare system. Apart from being mortal in some cases, this injury affects its victims’ quality of life as it is followed by many gastrointestinal problems. This injury mainly occurs accidentally among children, whereas in adults, this injury often occurs with suicidal intentions. Despite the recent advances in internal medicine, gastroenterology, and toxicology, this type of injury remains a debilitating and, in some cases, mortal disorder for its victims. Compared to the prevalence and complications, there is still limited evidence in this regard.

Materials and methods: This study retrospectively evaluated the clinical, laboratory, and endoscopic findings of 150 patients admitted to a referral center of toxicology and forensic medicine and assessed factors associated with each type of injury.

Results: we calculated a mortality rate as high as 7.3% in this population. Age, pH, and previous medical conditions were associated with more complications. Besides, higher degrees of injury were significantly associated with higher mortality, no significant difference was inspected between the types of corrosive substances.

Conclusion: It seems that the most effective intervention for controlling these types of injuries would be psychiatric support, primary health care, and household education.

A Predictive Factors of Inadequate Bowel Preparation for Elective Colonoscopy

Amir Sadeghi, Mohsen Rajabnia, Mohammad Bagheri, Shaghayegh Jamshidizadeh , Samane Saberi, Paria Shahnazi, Leila Pasharavesh, Mohamad Amin Pourhoseingholi, Mona Mirzaei, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Background: Inadequate bowel preparation can lead to lower polyp detection rates, longer procedure times, and lower cecal intubation rates. This study was aimed to evaluate the effects of factors like demographic items, comorbidities, and drug history on the inadequacy of colonic preparation before colonoscopy.

Methods: This population-based study was conducted on 2476 Iranian adults who were referred to two tertiary centers for elective colonoscopy between 2017 and 2018. Bowel preparation quality was scored by the Boston bowel preparation scale (BBPS). Univariate and multivariate logistic regressions were used to find the independent predictors of bowel preparation inadequacy.

Results: Our results showed that 31.8% of our patients had inadequate bowel preparation before performing colonoscopy. Higher age, BMI>25, abdominal circumference>95 cm, low fruit consumption, and history of smoking were independently correlated with bowel preparation inadequacy, additionally, using NSAIDs and SSRIs were correlated with bowel preparation adequacy in multivariate regression analysis. Finally, age, gender, ethnicity, BMI, abdominal circumference, fruit consumption, smoking, NSAIDs, SSRIs, education, constipation, physical activity, and diabetes entered our predictive model. The area under the curve (AUC) reached 0.70 in the final step.

Conclusions: We found the independent risk factors associated with colonic preparation inadequacy, and finally suggested a predictive model for identifying the patients with a high risk of bowel preparation inadequacy before performing a colonoscopy to employ alternative preparation techniques among high-risk groups, to yield optimal preparation quality.

Evaluation of nitric oxide and inducible nitric oxide synthase levels in patients with erosive esophagitis and non-erosive reflux disease

Fatemeh Nejat PishKenari, Durdi Qujeq, Seyed Saeid Mohammady Bonahi, Mehrdad Kashifard, Karimollah Hajian -Tilaki

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,


Background: Gastro-esophageal reflux disease (GERD) is one of the most common disturbances of the upper digestive tract. Inducible nitric oxide synthase (iNOS) is expressed in the esophageal adenocarcinoma. Nitric oxide (NO), the product of this enzyme, has been implicated in the pathogenesis of this condition. Nevertheless, there are conflicting data on whether iNOS and NO are expressed in the early stages of GERD.

Aim: This article aimed at evaluating NO (nitrite, nitrate) and iNOS markers in patients with erosive esophagitis (EE) and non-erosive reflux disease (NERD) compare them with the control group.

Methods:In this study, tissue samples were obtained from fifty four patients (27 erosive esophagitis and 27 non-erosive reflux disease), and 27 controls. Tissue concentrations of nitrite, nitrate, and iNOS were measuredusing Enzyme-Linked Immunosorbent Assay (ELISA).Also, the Bradford method was used to determine the protein concentration of samples. Our results were analyzed by SPSS software (Version 22.0). In multiple comparisons, the Tukey test was performed and the P < 0.05 was considered as the significant level.

Results: Tissue amounts of iNOS were significantly higher (P = 0.001) in EE patients compared with the control group. Also, about this factor, there was a significant difference (P = 0.01) between EE patients compared to patients with NERD. Moreover, tissue levels of nitrite and nitrate were significantly higher (P = 0.001) in patient groups compared with the control group.

Conclusion: We observed that NO and iNOS protein had increased in human esophagitis tissue.Our results indicated that nitric oxide and iNOS levels are useful and effective markers in the pathogenesis of GERD. Also, we do not know for sure but we'll probably there was a link between the expressions of iNOS with disease progression.

Introducing AKT1 as a Critical Common Dysregulated Proteins in Esophageal, Gastric, and Intestinal Cancers

Mostafa Rezaei –Tavirani

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Aim: The aim of this study is determining the common dysregulated proteins between esophageal, gastric, and intestinal cancers.

Background: There are several documents about role of AKT1 in promotion of esophageal, gastric, and intestinal cancers.

Methods: Number of 100 proteins related to each of esophageal, gastric, and intestinal cancers were retrieved from STRING database and interacted by Cytoscape software v 3.2.7. 2 to create the correlated interactomes. Results of network analysis and action map assessment were used to determine the common critical proteins between the three studied cancers.

Results: Among 42 common dysregulated proteins 36 individuals were selected via network analysis which were screened via action map assessment and 18 ones were introduced as the important common proteins. Finally, AKT1 was candidate as the crucial dysregulated proteins common the three analyzed diseases.

Conclusions: finding indicates that AKT1 is a suitable candidate to be evaluate in patients as a pre diagnostic tool to reduce endoscopy and colonoscopy rate.

Case Report

Therapeutic impact of determination of RAS mutations in the plasma of patients with colorectal cancer

Filipa Macedo, Joana Monteiro, Tatiana Cunha Pereira, Ana Raquel Monteiro, Rita Félix Soares, Nuno Bonito, Gabriela Sousa

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,

Introduction: Stage IV colorectal cancer treatment include targeted therapy depending on RAS status. During disease progression, loss or gain of RAS mutations could happen, supporting the hypothesis of evolutionary pressure of therapy. Circulating tumor DNA (ctDNA) are nucleic acids released to the bloodstream by the tumor during its development and could be detected by liquid biopsy.

Methods: The Idylla© Biocartis, a fully automated real-time-PCR based molecular diagnostic system, was used in a patient with metastatic colorectal cancer with a NRAS mutation in progression after several therapeutic lines.

Results: The ctDNA mutational analysis was performed and revealed the absence of mutations in KRAS, NRAS, and BRAF genes. The patient started the third line of palliative chemotherapy with irinotecan + cetuximab and achieved for the first-time partial response.

Conclusion: The authors describe a case were liquid biopsy determined the higher progression free survival achieved.

Right-sided aortic arch with aberrant left subclavian artery diagnosed by barium imaging in an87 day-old infant with regurgitation

Amirhossein Hosseini, Farid Imanzadeh, Mahsa Rashid, Ali Taher Ghasemi, Fatemeh Salahshouri, Fariba Alaei, parin Yazdanifard

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 1 (2022), 30 January 2022,


Right-sided aortic arch with aberrant left subclavian artery is a rare congenital anomaly of the aorta that occurs in less than 0.1% of population. They are asymptomatic in most of the cases and found incidentally, but can be symptomatic by compressing other structures like mostly trachea and esophagus. In this report, we present a case of esophageal compression by a right-sided aortic arch with aberrant left subclavian artery that mimicked an gastro-esophageal reflux in an 3 month-old (87 day-old) infant with complain of regurgitation, vomiting and failure to weight gain that was diagnosed by barium meal study.