Systematic Review and Meta-Analysis

Prognostic value of HIF-1α in digestive system malignancies: Evidence from a systematic review and meta-analysis

Mohammad-Hassan Arjmand, Ali Moradi, Hamidreza Rahimi, Ali Es-haghi, Abolfazl Akbari, MohammadReza Hadipanah, Jalil Afshar, Hassan Mehrad-Majd

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Background/aims: Numerous studies have demonstrated that hypoxia-inducible factor-1α (HIF-1α) is abnormally expressed in various solid tumors. However, the clinicopathological features and prognostic value of HIF-1α expression in patients with digestive system malignancies remain controversial. Accordingly, this meta-analysis was aimed to evaluate the association of HIF-1α expression with clinicopathological features and overall survival (OS) of patients with digestive system malignancies.

Methods: A literature search in PubMed, Web of Science, and Scopus databases was performed to identify all relevant studies published in English until 15 October 2020. Pooled effect was calculated to evaluate the association between HIF-1α expression and clinicopathological features and overall survival in cancer patients. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (CI) were calculated using either fixed- or random-effects model.

Results: A total of 44 eligible studies with 5,964 patients were included. Pooled results indicated positive correlation of HIF-1α overexpression with poor overall survival (OS) (HR=1.990, 95% CI: 1.615-2.453, P<0.001) and disease free survival (DFS) (HR=1.90, 95% CI: 1.084-3.329, P=0.043). Meta-results showed that HIF-1α level expression was significantly associated with positive lymph node metastasis (OR=1.869, 95% CI: 1.488-2.248, P<0.001), distance metastasis (OR=2.604, 95% CI: 1.500-4.519, P<0.001), tumor stage (OR=1.801, 95% CI: 1.437-2.257, P<0.001) and tumor size (OR=1.392. 95% CI: 1.068-1.815, P=0.014). 

Conclusions: This meta-data suggest that HIF-1α expression might serve as an independent prognostic marker and a promising therapeutic target in patients with digestive system malignancies.

Original Article

Multi-stage analysis of FOXM1, PYROXD1, hTERT, PPARA, PIM3, BMI1 and MCTP1 expression patterns in colorectal cancer

Samira Shabani, Elahe Elahi, Mandana Bahraniasl, Pegah Babaheidarian, Alireza Sadeghpour, Tayebeh Majidzadeh, Atefeh Talebi, Frouzandeh Mahjoubi

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: To explore biomarkers with a tumor stage-dependent expression pattern in patients with colorectal cancer (CRC).

Background: The fourth most common cancer in the world is colorectal cancer (CRC). A variation in the gene expression rate is a common change in cancers initiation and the accumulation of these variation changes the behavior of normal cells and turns them into cancer cells.

Methods: Real-time RT-PCR was used to investigate the expression patterns of the FOXM1, PYROXD1, hTERT, BMI, PPARA, PIM3 and MCTP1 genes in 54 patients with stage I to IV CRC and their relation with clinicopathological features of CRC were analyzed.  Results: FOXM1, hTERT and MCTP1 genes are overexpressed in CRC tumor tissues when compared to normal adjacent tissues in all the stages.  

Results FOXM1, PYROXD1, hTERT, PIM3, BMI1, PPARA and MCTP1 had-stage dependent expression. Investigation of the association between clinicopathological features and expression pattern of the studied genes revealed; a) a significant relationship between FOXM1 gene expression level and tumor stage, tumor size and lymph node involvement, b) a considerable association between alterations in PPARA and PIM3 expression and lymph node involvement, c) a notable correlation between hTERT expression level and the tumor stage and d) a strong correlation between MCTP1 expression  and patient's age only.

Conclusion: Our study indicates that expression profiles of these genes either individually or together can be applied as potential biomarkers for prognosis of CRC.

Clinical significance of TRIM29 expression in patients with gastric cancer

Javad Farhadi, Jamshid Mehrzad, Hassan Mehrad-Majd, Alireza Motavalizadehkakhky

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: The present study aimed to evaluate the expression profile, prognostic value, and possible correlation of TRIM29 with β-catenin, Cyclin D, and Bcl2 in Iranian patients with GC.

Background: Tripartite Motif Containing 29 (TRIM29) has been reported to function as an oncogene or a tumor suppressor depending on the tumor type. This contextual function has created a controversial situation that needs to be fully delineated in various cancers. Although few studies have reported an elevated TRIM29 expression in gastric cancer (GC), its clinicopathological and prognostic values as well as possible molecular mechanisms are yet to be re-evaluated in different populations.

Methods: Real-time quantitative PCR was used to detect TRIM29, β-catenin, Cyclin D, and Bcl-2 expression in 40 GC and their adjacent normal tissues. Patients were further stratified into high and low expression subgroups based on their TRIM29 expression levels. The association of TRIM29 expression level with β-catenin, Cyclin D, BCL2, some clinicopathological features, and patients' overall survival (OS) was assessed using appropriate statistical analyses.

Results The results showed a significantly higher TRIM29 expression level in GC tissues compared with their corresponding normal tissues (fold change=2.94, p=0.003). Patients with high TRIM29 expression levels exhibited poorer OS (HR=1.25, 95% CI: 1.06-1.47, p=0.007). High expression of TRIM29 was also associated with increased levels of β-catenin, Cyclin D, and Bcl-2 genes expression.  

Conclusion: Overexpression of TRIM29 is associated with poor prognosis in patients with GC and is probably mediated through β-catenin/Cyclin D/Bcl2 pathway and can be considered as a potential independent prognostic marker.

Cartilage Oligomeric Matrix Protein as a Non Invasive Biomarker for Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Hala A Abdel-Azeez, Hoda A Elhady, Abeer A Fikry

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: The current study purposed to evaluate serum COMP (Cartilage oligomeric matrix protein) as a diagnostic marker for HCC in patients with cirrhosis and to correlate it with other parameters of disease progression.

Background: COMP is known to promote fibrosis in various tissues. Emerging evidence shows that COMP plays critical roles in tumor development. It can serve as a fibrosis and cancer biomarkers.

Methods: The study included 24 subjects who serve as the healthy control, 24 cirrhotic patients without HCC, and 24 HCC patients with cirrhosis. All participants were subjected to liver function tests, AFP, calculation of fibrotic indices (APRI and FIB-4), and serum COMP by ELISA.

Results COMP was significantly increased in cirrhotic patients when compared to healthy controls and in HCC patients when compared to cirrhotic patients and healthy controls. A significant positive correlation was observed between COMP and APRI and FIB-4 in cirrhotic and HCC patients. Based on receiver operating characteristic (ROC) curve analysis, COMP had an area under curve (AUC) of 0.943 with 87.5% sensitivity and 79.2% specificity for diagnosis of HCC in cirrhotic patients. In combination with AFP, the sensitivity was increased to 100%.

Conclusion: COMP might act as a promising non-invasive biomarker for HCC either alone or in combination with AFP. It was correlated with the degree of fibrosis and associated with advanced cancer staging.

The efficacy and safety of furazolidone-bismuth quadruple therapy for Helicobacter pylori eradication with or without probiotics supplementation

Nafeh Noorbakhsh, Shahriar Nikpour, Mohammad Salehi

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: In this clinical trial we use furazolidone-bismuth quadruple therapy with or without probiotics for H.pylori eradication.

Background: Increasing rates of eradication failure in H.pylori infection mainly due to antibiotic resistance has led to search for alternative regimens such as using novel antibiotics and/or using probiotic supplementation as conjunctive to the standard eradication regimens.

Methods: This double blind clinical trial was performed in gastrointestinal clinic of Loghman Hakim University Hospital, Tehran, Iran. Patients with a positive pathology test for H.pylori were enrolled to the study and received a 14 day course of furazolidone 100 mg q.i.d, bismuth 240 mg b.i.d, amoxicillin 1000 mg b.i.d, pantoprazole 40 mg b.i.d plus either probiotic (Familact) b.i.d or placebo b.i.d. Adverse effects and adherence to therapy were evaluated at the end of the treatment course. Eradication was established by H.pylori fecal antigen test.

Results A total of 200 patients entered the study and were randomly assigned to two groups of placebo and probiotic. There was no significant difference regarding age or gender between placebo and probiotic groups. Adherence to therapy was higher than 90% in total and not significantly different between placebo and probiotic groups. Total eradication rate was 80.5% (n=161). Eradication rate was 84% in probiotic group vs 77% in placebo group (P=0.2). Total rate of adverse effects was 30% in probiotic group vs 62% in placebo group. The most common adverse effects were abdominal pain (15% in probiotic group vs 28% in placebo group, P=0.03) followed by diarrhea (5% in probiotic group vs 12% in placebo group, P=0.1).

Conclusion: According to our results, adding probiotic to furazolidone-bismuth quadruple therapy did no increase the eradication rate significantly. However, adverse effects particularly abdominal pain was lower in the probiotic group when compared with placebo.

Prevalence and outcome of COVID-19 among Iranian celiac patients

Fahimeh Sadat Gholam-Mostafaei, Nastaran Asri, Naser Parvani, Elham Aghamohammadi khamene, Farnoush Barzegar, Mohammad Rostami Nejad, Mostafa Rezaei-Tavirani, Bijan Shahbazkhani, Somayeh Jahani-Sherafat, Kamran Rostami, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: This study aimed to evaluate the prevalence and outcome of COVID-19 among Iranian celiac disease patients.

Background: Patients with celiac disease (CD) might be at greater risk for opportunistic viral infections. Coronavirus disease-2019 (COVID-19) is a new coronavirus (SARS-CoV-2) cause of respiratory disorder which spread around the world at the end of 2019. The question is does COVID-19 infection increase the risk of severe outcome and/or a higher mortality in treated celiac disease?.

Methods: Data regarding demographic details, clinical history, and COVID-19 infection symptoms among treated celiac disease patients was collected from July 2020 to January 2021 and analyzed using SPSS version 25.

Results A total of 455 celiac disease patients were included in this study. The prevalence of Covid-19 infection among celiac disease patients was 2.4%. Infection among women (72.7%) was higher than the men, and only one overweight man who smoked was hospitalized. Among COVID-19 infected celiac disease patients, the most common symptoms were myalgia 90.9% (10/11), fever, body trembling, headache, shortness of breath, loss of smell and taste, and anorexia (72.7%). Treatments for COVID-19, included antibiotics (90.9%), pain analgesics (54.5%), antihistamines (27.3%), antivirals (9.1%) and hydroxychloroquine (9.1%).

Conclusion: This study shows that treated celiac disease is not a risk factor for severity or higher mortality in patients infected with COVID-19. Women, however, might need extra-protection to prevent COVID-19 infection.

A systems biology analysis protein-protein interaction of digestive disorders and Covid19 virus based on comprehensive gene information

Arghavan Hosseinpouri, Mostafa Rezaei-Tavirani, Elham Gholizadeh, Reza karbalaei

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: Analysis of networks of digestive disorder and their relationship with Covid-19 based on systems biology methods, evaluation similarity, and usefulness of networks to give a new treatment approach.

Background: Digestive disorders are typically complex diseases associated with high treatment costs. They are related to the immune system and inflammation. With the outbreak of Covid-19, this disease was shown to have signs like diarrhea. Some signs of Covid-19 are similar to those of digestive disorders, like IBD and diarrhea. Both of them are accompanied by inflammation and induce disorders in the digestive system.

Methods: DisGeNET and STRING databases were sources of disease genes and constructing networks and were used to construct the network of digestive diseases and Covid-19. Three plugins of Cytoscape software, namely ClusterONE, ClueGO, and CluePedia, were used to analyze cluster networks and enrichment pathways. To describe the interaction of proteins, information from KEGG pathway and Reactome was used.

Results According to the results, IBD, gastritis, and diarrhea have common pathways. The CXCL8, IL-6, IL-1β, TNF-α, TLR4, and MBL2 molecules were identified as inflammatory molecules in all networks.

Conclusion: It seems that detecting genes and pathways can be useful in applying new approaches for treating these diseases.

High occurrence of Blastocystis subtype 3 in individuals referred to medical laboratories in Kermanshah, West of Iran

Bahman Maleki, Javid Sadraei, Abdolhossein Dalimi Asl, Majid Pirestani

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: The current study investigated the prevalence and genotypes of Blastocystis sp. in individuals who referred to medical laboratories in Kermanshah, Iran.

Background: Blastocystis sp. is a common intestinal protozoan found in humans and a wide range of animals, and it is involved in the development of gastrointestinal disorders.

Methods: A total of 950 stool samples were examined using the standard formalin-ether concentration technique. All specimens were cultured in Robinson xenic medium. Subsequently, DNA extraction and PCR amplification of subtype specific sequence-tagged site (STS) were conducted.

Results Microscopic examination showed that 86 out of 950 samples (9.05%) were infected with Blastocystis sp. Subsequently, 33 of 86 positive samples were cultured and molecularly confirmed by conventional PCR, indicating six subtypes (ST1-ST6). Of note, ST3 (45.0%) was the predominant subtype, followed by ST1 (15.15%) and ST5 (12%).

Conclusion: Based on the current findings, ST3 was the most frequent subtype among all positive samples. Having a better understanding of Blastocystis sp. subtype distribution and risk factors would lead to improved preventive measures.

Efficacy of 14-day concomitant quadruple therapy and 14-day high-dose dual therapy on H. pylori eradication

Behsood Yadollahi, Seyed Mohammad Valizadeh Toosi, Zohreh Bari, Hafez Fakheri, Iradj Maleki, Tarang Taghvaei, Vahid Hosseini, Arash Kazemi, Hajar Shokri-Afra

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Aim: We compared the efficacy of two different regimens for H. pylori eradication in areas with high antibiotic resistance.

Background: Helicobacter pylori (H. pylori) is a gram-negative bacillus that has a strong association with chronic gastritis and peptic ulcer disease. Different regimens with varying degrees of effectiveness have been used for H. pylori eradication.

Methods: The current randomized controlled trial (RCT) randomly assigned 217 patients who had indications for H. pylori eradication therapy to two groups. One group were administered concomitant quadruple therapy (pantoprazole 40 mg, amoxicillin 1 gr, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) for 14 days, and the second group received 14 days of high-dose dual therapy, consisting of esomeprazole 40 mg BID and amoxicillin 1g TDS. H. pylori eradication was assessed eight weeks after the end of treatment.

Results H. pylori eradication rates by PP analysis for 14 days concomitant quadruple therapy and high-dose dual therapy were 88.6% (95% CI, 80.3−92.8) and 82.2% (95% CI, 74.8–89.5), respectively (p = 0.19). According to intention-to-treat (ITT) analysis, the eradication rates were 81.6% (95% CI, 74.5−88.6) and 80.6% (95% CI, 73–88.1), respectively (p = 0.58). Overall drug side effects were 20.8% in high-dose dual therapy and 49.6% in concomitant quadruple therapy (p < 0.001).

Conclusion: Fourteen days concomitant quadruple therapy can be considered as a relatively acceptable regimen for H. pylori eradication in areas with high clarithromycin and metronidazole resistance. It seems that high-dose dual therapy could be a promising alternative regimen in these areas.

Case Report

A case of posterior reversible encephalopathy syndrome during endoscopic retrograde cholangiopancreatography after anesthesia

Amir Sadeghi, Isa Bakhshandeh Moghadam, Azita Hekmatdoost, Niloufar Salehi, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder that occurs following cerebral vasogenic edema. It has diverse clinical presentations from headache and vomiting to seizure and mental status alteration. Herein, we report a 54-year-old woman with no prior disease who developed PRES in the parieto-occipital lobes and brain stem after a second attempt endoscopic retrograde cholangiopancreatography (ERCP). To our knowledge, no case of PRES during ERCP has been reported to date. This case reminds us of unusual complications that are likely to occur after ERCP. It is believed that blood pressure fluctuations and anesthetic medications, fentanyl in particular, were the main precipitating factors causing the syndrome in the current case. Even if there is no specific treatment for this condition, a diagnosis is critical to start supportive treatment.

Transverse colon varices

Behzad Hatami, Naghmeh Salarieh, Pardis Ketabi Moghadam, Mehran Mahdavi, Azam Farahani

Gastroenterology and Hepatology from Bed to Bench, Vol. 15 No. 2 (2022), 15 Esfand 2022,

Portal hypertension associated with liver cirrhosis usually leads to gastroesophageal varices; however, ectopic varices secondary to liver cirrhosis are not common, especially colonic varices which occur with a low frequency.

We are going to discuss the case of a 75-year-old man with liver (HBV) cirrhosis who was admitted to the hospital with rectorrhagia. Colonoscopy revealed evidence of acute bleeding in tortuous colonic varices. The band ligation performed during the colonoscopy had failed to control the bleeding.

The patient was referred to Taleghani Hospital in Tehran, and rectorrhagia was subsequently successfully controlled by BRTO technique (balloon-occluded retrograded transvenous obliteration).

Letter to Editor

We read with interest the article recently published in Gastroenterology and Hepatology from Bed to Bench entitled “The impact of COVID-19 Vaccination in Iranian elderly: 7 percent of all-cause deaths reduced by vaccinating 2 percent of population”. The aim of the paper was to predict the impact of vaccination of old population on all-cause deaths based on time series model.