Gastroenterology and Hepatology From Bed to Bench最新文献

Aim: A systematic review was conducted to summarize the methylated circulating tumor DNA (ctDNA) markers reported over the last decade for early detection of colorectal cancer (CRC) and to identify the main technical challenges that are impeding their clinical implementation.

Background: CRC is a major cause of cancer deaths worldwide, but early detection is key for successful treatment. Non-invasive methods such as methylated ctDNA testing show promise for improving detection and monitoring of CRC.

Methods: A comprehensive search was performed using Web of Science, PubMed, and Scopus up to December 30, 2023, limited to articles published in the last 10 years (after 2012), while including advanced adenoma/stage 0 or stage I/II samples in biomarker validation.

Results: After identifying 694 articles, removing duplicates and screening titles, abstracts, and full texts, a total of 62 articles were found to meet the inclusion criteria. Among the single biomarkers, MYO1-G, SEPT9, SDC2, and JAM3 revealed the highest sensitivity for polyps and stage I/II CRC. For multi-biomarkers with suitable sensitivity, combinations of SFRP1, SFRP2, SDC2, PRIMA1, or ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM or ZFHX4, ZNF334, ELOVL2, UNC5C, LOC146880, SFMBT2, GFRA1 were identified for polyps and stage I/II CRC.

Conclusion: Enhancing sensitivity and specificity of molecular screening methods is crucial for improving CRC detection. Identifying a select few valuable biomarkers is key to reducing costs, despite challenges posed by low ctDNA levels in plasma, particularly in early-stage cancers.

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 of age presenting with diarrhea at Mbagathi County Hospital were recruited. Stool microbiology test was used to detect Salmonella species. Polymerase chain reaction was employed 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 which 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 current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use.

Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors.

Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model.

Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses.

Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized.

Aim: This study aimed to compare dynamic thiol/disulfide homeostasis and myeloperoxidase (MPO) levels in patients with Gilbert's syndrome (GS) and healthy controls.

Background: Thiol/disulfide homeostasis and MPO levels are both associated with increased progression of atherosclerosis.

Methods: The study included a total of 130 voluntary participants comprising 65 patients with GS and 65 healthy controls. These patients were selected randomly and dynamic thiol/disulfide homeostasis, MPO, complete blood count results, and biochemistry and lipid parameters were evaluated. Patients with known chronic diseases, medication usage, and acute infections were excluded from the study. Serum total thiol and native thiol levels were measured using the fully automated colorimetric method, while serum MPO levels were measured using the sandwich ELISA method.

Results: We found that patients with GS had significantly higher total thiol (352.3±38.6 vs. 317.9±47.9, p<0.001) and native thiol (386.6±42.6 vs. 348.0±51.1, p<0.001) and significantly lower disulfide (15.7±4.0 vs. 17.3±4.0, p=0.022) and MPO (130.7 vs. 166.3, p=0.006). In patients with bilirubin of <1 mg/dL, total thiol and native thiol levels were lower and disulfide, disulfide/native thiol (DNT) and disulfide/total thiol (DTT) ratios, and MPO levels were higher. Patients with bilirubin of <1 mg/dL also had higher total cholesterol.

Conclusion: In these patients with GS, the thiol/disulfide balance shifted towards thiols and proinflammatory MPO levels were lower. When bilirubin was <1 mg/dL, disulfide, DNT and DTT ratios, and MPO were higher. Bilirubin levels affected all parameters of thiol/disulfide homeostasis and MPO levels independently of other risk factors. In light of our results, we suggest that mild hyperbilirubinemia in cases of GS has an anti-inflammatory and antioxidant effect and may be protective against atherosclerosis.

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: 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: We evaluated the response to Trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. We determined the prognostic value of the neutrophil-to-lymphocyte ratio (NLR).

Background: TACE is the most commonly used method to treat patients with large, unresectable tumors or as bridge therapy in patients with HCC before liver transplantation.

Methods: In this cross-sectional study, patients with a diagnosis of HCC who were referred for TACE were studied. The response rate to TACE treatment was assessed based on dynamic MRI 28 days after treatment according to mRECIST criteria. The NLR value was calculated, and its prognostic value was evaluated to predict the response to treatment.

Results: Forty patients with HCC who underwent TACE were included. The response to TACE treatment included a complete response (CR) in 6 patients (15%), partial response (PR) in 16 patients (40%), and stable disease (SD) in 18 patients (45%). No progressive disease (PD) was found. Responders (CR and PR) were 22 patients (55%). The mean NLR after treatment in the non-responders was significantly higher than in the responders (4.2 vs. 2.4, P-value = 0.026). NLR values greater than 2.6 after treatment had a sensitivity of 70.6% and a specificity of 77.3% in diagnosing non-responders, with an Area Under the Curve (AUC) of 0.73 [95% confidence interval 0.58-0.89], P-value = 0.011.

Conclusion: Non-responders observed higher levels of NLR after treatment than responders. As a moderate prognostic factor, an NLR level of more than 2.6 after treatment could discriminate against non-responders.

Aim: The purpose of this retrospective single-center study was to determine the frequency of sarcopenia and its association with mortality and other morbidities in children with chronic liver disease who had undergone liver transplantation.

Background: Sarcopenia, a muscle-wasting syndrome, is common in patients with advanced liver disease and is associated with increased morbidity and mortality. While sarcopenia in adults has been extensively studied, there is little information in this regard about children and adolescents with chronic liver diseases.

Methods: The study included 108 children and adolescents who had undergone liver transplantation. Sarcopenia was measured using skeletal muscle index at the third lumbar vertebral level and assessed using abdominal computed tomography imaging.

Results: The frequency of sarcopenia in the studied population was found to be 45.7%. Patients with sarcopenia were more likely to be male (P<0.0001), older (P<0.0001), and had lower height-for-age z-scores (P=0.012). Genetic/metabolic diseases were the most common underlying cause of sarcopenia in children. Except for a higher rate of transplant rejection in the sarcopenia group (P=0.035), there was no significant difference in mortality rates (P=0.688) or post-LT complications between the two groups. One year after LT, computed tomography-derived body composition parameters revealed no significant differences between children who survived and those who did not.

Conclusion: Our findings indicated a high frequency of sarcopenia in children with chronic liver disease, implying that more research is needed to better understand its impact on clinical outcomes in this population.

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. Hepatic encephalopathy, Carnitine, Ammonia, Genetic, Treatment.

Hepatocellular carcinoma (HCC) typically presents with a primary hepatic mass. Nevertheless, on rare occasions, the initial presentation can be exclusively related to extrahepatic metastases and the most common sites of metastases are the lungs, lymph nodes, bones, and adrenal glands. While, bone metastases are generally accompanied by multiple metastatic spreads elsewhere in the body or previously diagnosed HCC, cases of solitary bone metastases with no liver lesion at imaging have been reported. Indeed, two rare entities of HCC have been reported in the literature which are the ectopic hepatocellular carcinoma and the infiltrative type of hepatocellular carcinoma with a very challenging radiologic diagnosis and poor prognosis. In this article, we present a case of extrahepatic costal metastases of hepatocellular carcinoma, which was diagnosed through a bone biopsy, with no focal lesion on liver imaging including ultrasound, multiphase MRI, and CT scan except for the presence of a portal vein thrombosis. It is important to consider the possibility of HCC metastases when evaluating rapidly growing extrahepatic lesions in patients with chronic liver disease and to consider the tumor characteristics and imaging findings as well as limitations to make accurate and timely diagnosis leading to improved patient management. Our patient had probably an infiltrating HCC because of two prominent factors: the presence of portal vein thrombosis and a markedly elevated alpha-fetoprotein (AFP). A liver biopsy was crucial in order to confirm the diagnosis but unfortunately it could not be performed because of the unexpected death of the patient due to hemorrhagic shock. It is also worth noting in this case, that the elevated level of AFP raised the suspicion on an underlying HCC and contributed to more elaborate diagnostic tests.