Gastroenterology and Hepatology from Bed to Bench

Dear Editor

This letter would breafly focused the worlwide attention to a very recently debat: the correct use of DGP IgG in childern under two years aged. We recently pubblished an article in this journal in which we demontrated the essential role of DGP-IgG for Celiac diagnosis in newborn. Now Catassi, one of the most prominent exponents, invite us to review the diagnostic approach  and finally review the clinical guideline

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.

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

Background: As validated biomarkers for predicting the clinical outcomes of gastric cancer (GC) have not been fully investigated, the present cross-sectional study has aimed to evaluate the prognostic value of tripartite motif-containing 29 (TRIM29) in GC patients.

Methods: The real-time quantitative PCR method was used to detect TRIM29, β-catenin, Cyclin D, and Bcl-2 expression in 40 gastric cancer tissues and adjacent normal tissues. Association of TRIM29 expression level with some clinicopathological features and patients' overall survival (OS) was assessed using several statistical analyses including, Pearson’s correlation test, Kaplan–Meier method, and Cox regression.

Results: Our results showed that TRIM29 expression level was significantly lower in GC tissues compared with that in the corresponding normal tissue (fold change=0.34, p=0.003). In subgroup analysis based on the TRIM29 expression, patients with low TRIM29 expression level exhibited poorer overall survival (HR = 1.25, 95% CI: 1.06-1.47, p=0.007). Low expression of TRIM29 were also associated with increased level of β-catenin, Cyclin D, and Bcl-2 genes expression.

Conclusion: It was concluded that down-regulated expression of TRIM29 is associated with poor prognosis in patients with gastric cancer. TRIM29 may play a protective role in malignant progression of gastric cancer by relieving the effects of cancer progressive genes and could be considered as an independent prognostic marker.

Background: Cartilage oligomeric matrix protein (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.

Aim: To evaluate serum COMP as a diagnostic marker for HCC in patients with cirrhosis and to correlate it with other parameters of disease progression.

Subjects and Methods:  The study included 24 subjects who serve as healthy control, 24 cirrhotic patients without HCC and 24 HCC patients on top of cirrhosis.All participants were subjected to determination of 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. On 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 was associated with advanced cancer staging.

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

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).

Discussion: 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.

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 at the end of 2019. The question is whether COVID-19 infection would increase the risk of severe outcome and or a higher mortality in treated celiac disease? This study aimed to evaluate the prevalence and outcome of COVID-19 among Iranian celiac disease patients.

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

Results: A total of 455 celiac disease patients were included in this study. Prevalence of Covid-19 infection among celiac disease patients was 2.4%. Infection among women (72.7%) was higher than the men, and only a smoker man who was overweight 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 & taste, and anorexia (72.7%). Treatments for COVID-19, included antibiotics (90.9%), pain analgesics (54.5%), antihistamines (27.3%), antiviral (9.1%) and hydroxychloroquine (9.1%).

Conclusion: This study shows treated celiac disease is not a risk factor for severity or higher mortality when infected with COVID-19. The women might need extra-protection to prevent the COVID-19 infection

Aim: Analysis reconstruction networks from digestive disorder and their relationship to Covid19 based on systems biology methods.

Background: The digestive disorders typically are complex diseases with high costs for treatment. Sometimes related to the immune system and inflammation. With the outbreak of Covid19, it was showed has signs like diarrhea. Totally some signs of Covid19 are similar to digestive disorders like IBD and diarrhea. Both of them with inflammation induce disorders in the digestive system. 

Methods: common genes between Covid19 and digestive disorders like IBD, gastritis, diarrhea construct network. Common genes between IBD, diarrhea, and gastritis were extracted and imported to STRING database to construct PPI network. The resulting network contained 219 nodes and 4932 edges.

Conclusion: Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. designing PPI network can be the goal for drug designing and introducing diseases novel treatments.

Aim: The purpose of this study was to investigate the prevalence and identification of different subtypes of Blastocystis in individuals referred to medical laboratories in Kermanshah, West of Iran.

Background: Blastocystis is a common intestinal anaerobic unicellular eukaryote parasite that was found in human and a wide range of animals. Nowadays, it has been suggested that some Blastocystis subtypes are involved in the development of gastrointestinal disorders.

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

Results: Of the 950 samples tested by microscopic survey, 86 (9.05%) samples were infected with Blastocystis. 33 samples (38%) of microscopic positive cases were grown in culture medium and all of them were confirmed by conventional PCR. In this regard, six subtypes of Blastocystis consisted (ST1, ST2, ST3, ST5, ST6 and ST7) were identified. Among them, Blastocystis ST3 (45.0%) was the predominant subtype, followed by ST1 (15.15%) and ST2 (12%).

Conclusion: The present study indicated ST3 subtype was the most prevalent subtype among the positive samples. Finally, the identification of subtype distribution can help to improve understanding of the risk factors.

Background: Helicobacter pylori (H. pylori) is a gram-negative bacillus that has strong association with chronic gastritis and peptic ulcer disease. H. pylori infection is difficult to treat, and successful treatment requires two or more antimicrobial agents. Different regimens with varying degrees of effectiveness have been used for H. pylori eradication. We compared the efficacy of two different regimens for H. pylori eradication in area with high antibiotic resistance.

Material and Methods: We performed a randomized clinical trial in which 217 patients who had indication for H. pylori eradication were assigned to two groups. One group were taken 14 days concomitant quadruple therapy (pantoprazole 40 mg, amoxicillin 1gr, clarithromycin 500 mg and metronidazole 500 mg every 12 hours for 14 days) and the other group received 14 days high-dose dual therapy, consisted of esomeprazole 40 mg, BID and amoxicillin 1g TDS. H. pylori eradication was assessed eight weeks after end of treatment.

Results: H. pylori eradication rates by per-protocol 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). Also, according to intention to treat 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). The overall drug Side effects was 20.8% in high-dose dual therapy vs. 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 of high clarithromycin and metronidazole resistance. It seems that the high-dose dual therapy could be a promising alternative regimen as the first line H. pylori eradication in these areas.

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. In this report we present a 54-year-old woman with no prior disease developed PRES in parieto-occipital lobes and brain stem after a second attempt ERCP. To our knowledge no case of PRES during ERCP has been reported yet. This case reminds us unusual complications that are likely to occur after ERCP procedure. It is believed that the blood pressure fluctuation and anesthetic medications, fentanyl in particular, were the main precipitating factors causing the syndrome in our case. Even if there is no specific treatment for this condition, a diagnosis is critical to start supportive treatment.

Portal Hypertention associated with liver cirrhosis usually leads to Gasteresophageal 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 about a 75-year-old man with liver (HBV) cirrhosis that was admitted to Hospital with rectorrhagia, colonoscopy revealed evidence of acute bleeding in tortuous colonic varices. The bandligation performed during Colonoscopy which had failed in controlling the bleeding.

He was referred to Taleghani hospital in Tehran and successfully rectorrhagia was controlled by BRTO technique (balloon _occluded retrograded trans venous obliteration).

Dear 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.