Gastroenterology and Hepatology from Bed to Bench

Aim: This survey aimed to assess the differentiation of Gastric adenocarcinoma (GA) and pancreatic adenocarcinoma (PA) via immunohistochemistry biomarkers.

Background: GA and PA are two gastrointestinal malignancies with similarities in immunohistochemical features, making the diagnosis complex in some cases.

Methods: We searched international databases, including Google Scholar, Web of Science, PubMed, Embase, PROQUEST, and Cochrane Library, using appropriate keywords. The variance of each study was calculated using the binomial distribution formula, with all data analyzed by R version 16. Pooled odds ratios (OR), 95% confidence intervals (CI), and the I² test were calculated to evaluate the effectiveness of various immunohistochemistry biomarkers. Publication bias was assessed using funnel plots plus Begg’s and Egger’s tests.

Results: Based on the finding of our study, four potent biomarkers which can distinguish GA from PA were Cadherin 17 (CDH17) with pooled OR= 3.73 (95% CI 1.58 to 8.87), P value=0.003, and I2=55.5%; Caudal-type homeobox 2 (CDX2) with pooled OR=8.99 (95% CI 4.52 to 17.90), P value= <0.001, and I2=52.2%; CK7 with pooled OR= 0.15 (95% CI 0.04 to 0.57), P value= 0.005, and I2=56.6%; CK20 with pooled OR=2.06 (95% CI 1.38 to 3.08), P value= <0.001, and I2=0%.

Conclusion: Our study identified CDH17, COX-2, CK7, and CK20 as potent IHC biomarkers for differentiating PA and GA. Incorporating these biomarkers into routine diagnostics is essential for improving accuracy in challenging cases, ultimately aiding timely treatment decisions and improving patient outcomes.

Aim: This systematic review and meta-analysis aimed to assess the effect of hydrogen-rich water (HRW) on liver enzyme levels.

Background: Liver disease is a significant global health concern, greatly affecting mortality rates. Elevated levels of liver enzymes, such as ALT, AST, ALP, and GGT are early symptoms of liver disorders, and various approaches can help reduce them. Recent studies have shown the prospective therapeutic advantages of hydrogen as an antioxidant and anti-inflammatory agent in many circumstances.

Methods: The search strategy was developed following PRISMA guidelines. PubMed, Google Scholar, and Embase were searched from the beginning to January 2024. Eight Randomized controlled trial (RCT) studies were included, encompassing 433 participants with various liver function disorders. 

Results: Our results showed a slight decrease in ALT, AST, and ALP levels in the treated group with HRW compared to the PW group.

Conclusion: Our findings suggest that consuming HRW may decrease liver enzyme levels in clinical populations. Further research is needed to confirm this relationship.

Aim: We aimed to perform a systematic review to gather evidence on the efficacy of somatostatin analogs (SA) in managing bleeding gastrointestinal angiodysplasias (GIADs).

Background: Some usual treatment modalities for bleeding caused by GIADs include endoscopic or surgical management. However, considering their availability and side effects, they may not be feasible for every patient. On that account, pharmacological management may become a safe and effective option.

Methods: In January 2024, a systematic review of the literature was conducted using the PubMed/Medline, Cochrane Library, and Scopus databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) framework was followed. Inclusion in this review was restricted to randomized clinical trials (RCTs) or observational studies comparing the use of SA as the main or complementary therapy in patients with GIADs. The outcomes of interest were hemoglobin levels, transfusion requirements, bleeding, and safety/adverse effects.

Results: Seven studies were included in the systematic review, two RCTs and five observational studies. There were 682 patients, of which 166 (24.3%) received any form of treatment involving SA. The studies varied greatly regarding follow-up, SA of choice, and other treatments associated with SA or as a control. Lanreotide appears to be able to significantly improve hemoglobin levels when associated with various treatments, whereas octreotide does not. One RCT found a significant reduction in blood or iron transfusion units when comparing SA to a standard of care, but other studies had mixed results. Lanreotide may be useful in reducing bleeding episodes in patients treated with argon plasma coagulation with double-balloon enteroscopy. Gastrointestinal adverse events such as diarrhea, vomiting, and abdominal pain were commonly reported across studies.

Conclusion: The majority but not all included studies suggest that SA may improve hemoglobin levels and reduce bleeding in patients with GIAD. However, the studies included small sample sizes and were not of strong statistical power. Further RCTs with larger populations are necessary to validate the effectiveness of SA in managing patients with GIAD.

Hepatic encephalopathy (HE) is a serious neurological disorder characterized by brain dysfunction due to liver failure which occurs as a result of chronic or acute liver disease. HE can manifest with various neurological or psychiatric symptoms ranging from excessive sleepiness and sleep disorders to coma. HE is a serious disorder that in acute conditions can even lead to the death of the patient due to cerebral edema. Carnitine acts as a vital component in facilitating the transport of long-chain fatty acids into the mitochondria, thereby enabling their oxidation for the generation of energy. Carnitine additionally assumes a crucial role in the functionality of the brain. Carnitine deficiency is associated with various types of inherited disorders related to low levels of carnitine. A strong correlation exists between the insufficiency of carnitine and the occurrence of HE. If a deficiency of carnitine is identified through clinical symptoms or laboratory results in patients with liver dysfunction, treatment with carnitine replacement therapy is recommended. Thus, the administration of acetyl-L-carnitine in patients with HE can improve their mental and psychological conditions. In the present study, we provide an overview of the molecular and cellular mechanisms underlying HE. Our aim in this review has been genetic investigation of HE and genetic mutations to the causes of this neurological condition, which include carnitine deficiency, hyperammonemia, and etc. Finally, we discuss the genetic mutations that lead to carnitine deficiency as well as hyperammonemia and are associated with this neurological disease, together with the future treatment of this disease based on carnitine therapy. More studies soon will help early diagnosis (before poor prognosis) based on clinical observations, genetic tests, prenatal diagnosis, and new treatment strategies.

Continuing studies related to Abdominal Compartment Syndrome (ACS) is imperative in terms of its significant effect on morbidity and mortality rates. To establish bibliometric analysis as a comprehensive review of ACS literature. The process encompasses many phases, such as delineating search terms, beginning and refining search results, creating preliminary statistics from the data, and performing data evaluation. Scopus database was selected as the primary source, and VOSviewer software was used to visualize author networks, country affiliations, journal affiliations, and keyword associations. The analysis was conducted on January 16th, 2023, and yielded a total of 855 documents spanning the period from 1993 to 2022. Studies on ACS showed an annual increase, but it has not yet reached a mature stage. United States leads the world in terms of the highest number of publications, h-index, citations, and the involvement of renowned authors and organizations. Through an analysis of less frequently used keywords, this study identified potential themes for future investigation, including histopathology, biological markers, interleukin 6, alanine aminotransferase, early diagnosis, scoring systems, the severity of illness indices, clinical practices, patient monitoring, preoperative evaluations, minimally invasive surgery, inter-method comparisons, multicenter studies, follow-up investigations, systematic reviews, and meta-analyses. While publications in ACS journals are crucial, they alone are not exhaustive, necessitating further research.

Aim: The present study presents a new combined approach for the treatment of irritable bowel syndrome (IBS), in which the effect of Cognitive Behavioral Therapy (CBT) based on exposure to awareness and emotional expression on patients' symptoms is examined.

Background: IBS is one of the most common functional gastrointestinal diseases where psychological distress is an integral part of its presentation.

Methods: We performed a clinical trial study on 30 patients with IBS. They were divided into two groups receiving the intervention and waiting list control. All patients were evaluated by IBS quality of life scale, IBS severity score, hospital anxiety and depression scale and visceral sensitivity index in three stages: pre-test, pre-test, and one-month follow-up. Our treatment program for the intervention group (n=15) included 10 group sessions, every week for 90 minutes, based on an exposure-based cognitive behavioral therapy protocol. Also, they underwent three 90-minute sessions of an emotional expression and awareness training program.

Results: The mean age of the participants was 31.0±8.77 years old. No previous history of substance addiction, psychiatric, or neurologic diseases was seen. Twenty participants (66.7%) were single, twenty-three participants (76.7%) had a university degree, and 9 participants were unemployed. No significant difference was seen between the case and control groups regarding education, occupation, and marital status. All pairwise comparisons of pre-test, post-test, and follow-up IBS-QOL scores were significant between the two groups (p<0.001). Similarly, pre- and post-, and pre- and follow-up test differences for IBS-SSS and VSI were significantly different between the two groups.

Conclusion: Exposure-based CBT combined with emotional expression and awareness training could alleviate the IBS symptoms, reduce visceral sensitivity, and improve quality of life.

Aim: This study was conducted to discover the effect of NCAPD3 knockdown on the gene expression profile of gastric cancer. Background: Gastric cancer, a potentially fatal disease, requires thorough evaluation for targeted interventions. Through the post-analysis of microarray data, it is crucial to further examine the impact of NCAPD3 (Non-SMC condensin II complex subunit D3) inhibition in gastric cancer, emphasizing the need for a more comprehensive analysis of this knockdown.

Methods: Use of Cytoscape and its plug-ins for protein-protein interaction network analysis enables the identification of genes that significantly affect network stability. These hub-bottlenecks are regulated due to the NCAPD3 inhibition and some of them act as compensators in this condition. The hub-bottlenecks pathways identified by ClueGO indicate their relationships in underlying mechanisms of knockdown. These identified central differentially expressed genes could be considered eligible targets for therapeutic interventions. Some of them play compensative roles while others are regulated in NCAPD3 knockdown.

Results: It can be concluded that some of the hub-bottlenecks contribute to compensation mechanisms including NPM1, PTEN, EGFR, HSPA5, and ASNS, while the other ones including HSPA4, DHX9, CAV1, MAP1LC3B, and SRSF1 are among the regulated genes.

Conclusion: In particular, the up-regulation of EGFR and ASNS genes in the knockdown scenario could significantly impact and deteriorate cancer treatment outcomes after comprehensive validation studies.

Aim: Our goal was to assess the need for vaccination and preventive measures in this vulnerable population.

Background: HAV is the most common form of acute viral hepatitis, transmitted primarily via fecal-oral route. Therefore, poor hygiene and close contact among institutionalized people are associated with higher HAV infection prevalence. We sought to determine the seroprevalence of anti-HAV antibodies among institutionalized individuals with intellectual impairments in light of Iran's falling trend in HAV antibody prevalence.

Methods: In this cross-sectional study, we evaluated the seroprevalence of total and IgM anti-HAV antibodies of 254 institutionalized people with intellectual disabilities. Total and IgM anti-HAV antibodies of the blood samples of these people were determined by ELISA method.

Results: The seroprevalence of total and IgM anti-HAV antibodies among institutionalized people with intellectual disability were 15.4% and 0.4% respectively. In comparison to other institutionalized patients, individuals who were elderly and had spent more time in the institutions exhibited a higher prevalence of anti-HAV antibodies (p-values= 0.011 and <0.001, for example).

Conclusion: Based on our study, intellectually disabled people have a low prevalence of anti-HAV antibodies, which increases with age and the duration of institutionalization. Therefore, vaccination is necessary to prevent serious infection in these people.

Aim: To better understand the molecular mechanism of Helicobacter pylori (H. pylori) in adenocarcinoma, the gene expression profile of AGS cells was analyzed by complementary study.

Background: Gastric cancer, as one of the most lethal malignancies in the world, is important to be studied in terms of biomarkers. On the other hand, Helicobacter pylori is one of the key risk factors in this type of disease.

Methods: In this cross-sectional study, we evaluated the seroprevalence of total and IgM anti-HAV antibodies of 254 institutionalized people with intellectual disabilities. Total and IgM anti-HAV antibodies of the blood samples of these people were determined by ELISA method. Protein-protein interaction (PPI) network analysis is a bioinformatic study with validation values for biomarker identification and clarification of molecular mechanisms. Cytoscape V 3.10.2 and its application identified potential central elements of the PPI network and its corresponding roles

Results: GAPDH and P53 are the most promising candidates in this study. In addition, the microRNA signatures assessment provided more information about these biomarkers and added more value. 

Conclusion: Consequently, a new outlook for the relationship between gastric cancer and H. pylori was explored based on the new key biomarkers.

Aim: Molecular mechanism detection of stage I to stage II transition of esophageal squamous cell carcinoma via protein-protein interaction (PPI) network analysis is the main aim of this study.

Background: Esophageal cancer (EC) is recognized as cancer with a very poor prognosis and malignancy. It is characterized by a high prevalence rate within the world and a very low survival rate, even with treatment.

Methods: To detect esophageal squamous cell carcinoma (ESCC) related genes, gene expression profiles (GEPs) of GSE161533 from the Gene Expression Omnibus (GEO) database were considered to be analyzed. Data was evaluated via the GEO2R program to explore the significant differential genes (DEGs) associated to stages I and II of esophageal squamous cell carcinoma.  Each analysis's top 250 significant DEGs were evaluated, and the non-common genes were assessed via PPI network analysis. The hub-bottleneck DEGs were determined and enriched via gene ontology.

Results: Results indicate 373 significant DEGs discriminate stage I from stage II. PPI network analysis associated with gene expression assessment showed that COL1A1, SERPINE1, PDGFRB, AURKA, TGFBI, LGALS3, BRCA1, and TFRC are the critical DEGs which are related to ESCC transition state from stage I to II of disease. A total of 13 biological processes and molecular functions were related to the crucial genes.

Conclusion: In conclusion, the Upregulation of COL1A1, SERPINE1, PDGFRB, AURKA, TGFB1, and LGALS3 and downregulation of BRCA1 and TFRC in stage II of ESCC relative to stage I were pointed out as the key events which are associated with promotion of stage I to stage II transition.

Aim: To characterize salmonella virulent and antibiotic resistance genes in children with diarrhea in Nairobi city, Kenya. 

Background: Salmonella species carry virulent genes whose expression correlate with severity of salmonellosis.  Effective treatment of salmonellosis by antibiotics is threatened by expression of antibiotic resistant genes.

Methods: In a cross-sectional study, a total of 374 children below five years presenting with diarrhea at Mbagathi County Hospital were recruited.  Stool microbiology test was used to detect Salmonella species.  Polymerase chain reaction was used to detect virulent and antibiotic resistant genes.

Results: Salmonella species was isolated in 9 (2.4%) children.  A total of 9 (100.0%), 7(77.8%), 9 (100.0%) and 6 (66.6%) of the isolates harbored invA, Hila, sopB, and Stn virulent genes, respectively.  None (0.0%) of the isolates was resistant to gentamycin but 7 (77.8%), 7 (77.8%), 9 (100.0%), 8 (88.9%), 7 (77.8%), 6 (66.7%) and 5 (55.6%) of Salmonella species were resistant to ampicillin, ceftriaxone, streptomycin, ciprofloxacin, chloramphenicol, erythromycin and tetracycline, respectively. Ampicillin (citm), ceftriaxone (bla CMY), streptomycin (aadA1), gentamycin (aac(3)-IV), ciprofloxacin (qnr), chloramphenicol (catA1), erythromycin (ereA) and tetracycline (tetA) resistant gene was detected in 6 (85.7%), 6 (85.7%), 9 (100.0%), 8 (100.0%), 6 (85.7%), 6 (100.0%), and 5 (100.0%) of Salmonella isolates that were phenotypic resistant to ampicillin, ceftriaxone, streptomycin, ciprofloxacin, chloramphenicol, erythromycin and tetracycline, respectively.  

Conclusion: Salmonella species expressing virulent and antibiotic resistant genes is an important cause of gastroenteritis in children in Kenya

Aim: The purpose of the study was to assess benefits of oral midodrine in the role of primary prevention of hepatorenal syndrome (HRS) in Child-Turcotte-Pugh Class C (CTP-C) cirrhotics.

Background: The present non-randomized pilot study was designed for primary prevention of HRS as there is absence of an effective and definite treatment for this complication of cirrhosis to date other than liver transplant (LT).

Methods: This study effectively involved 30 patients each enrolled in interventional and control arms suffering from liver cirrhosis CTP-C with normal renal function and having a mean arterial pressure (MAP) < 80 mmHg who were subjected to clinical examination and baseline blood investigations. The mean daily dosage of midodrine used across the study group was 16.75 mg.

Results: At the end of 4 months of study, 11 individuals completed the study without attaining any endpoints from the control group while 23 accomplished it from the interventional arm. Nearly 50 % patients required a midodrine dose of 7.5 mg 8th hourly while the rest attained the targeted MAP with lower doses. By increasing MAP, the rate of HRS development during the study period (i.e. 4 months) was found to be significantly reduced in patients from interventional arm. The number needed to treat (NNT) observed in survival analysis to prevent one death was found to be 7.6.

Conclusion: This study successfully established the role oral midodrine in primary prevention of HRS in cirrhotics at high risk. Midodrine was well tolerated with no significant adverse effects in patients under study.