World Journal of Gastrointestinal Pathophysiology最新文献

Obesity is increasingly prevalent in the post-industrial era, with increased mortality rates. The gut microbiota has a central role in immunological, nutritional and metabolism mediated functions, and due to its multiplexity, it is considered an independent organ. Modern high-throughput sequencing techniques have allowed phylogenetic exploration and quantitative analyses of gut microbiome and improved our current understanding of the gut microbiota in health and disease. Its role in obesity and its changes following bariatric surgery have been highlighted in several studies. According to current literature, obesity is linked to a particular microbiota profile that grants the host an augmented potential for calorie release, while limited diversity of gut microbiome has also been observed. Moreover, bariatric surgery procedures represent effective interventions for sustained weight loss and restore a healthier microbiota, contributing to the observed fat mass reduction and lean mass increase. However, newer evidence has shown that gut microbiota is only partially recovered following bariatric surgery. Moreover, several targets including FGF15/19 (a gut-derived peptide), could be responsible for the favorable metabolic changes of bariatric surgery. More randomized controlled trials and larger prospective studies that include well-defined cohorts are required to better identify associations between gut microbiota, obesity, and bariatric surgery.

Background: The prevalence of Crohn's disease (CD) and ulcerative colitis (UC) is on the rise worldwide. This rising prevalence is concerning as patients with CD and UC may frequently relapse leading to recurrent hospitalizations and increased healthcare utilization.

Aim: To identify trends and adverse outcomes for 30 d readmissions for CD and UC.

Methods: This was a retrospective, interrupted trends study involving all adult (≥ 18 years) 30 d readmissions of CD and UC from the National Readmission Database (NRD) between 2008 and 2018. Patients < 18 years, elective, and traumatic hospitalizations were excluded from this study. We identified hospitalization characteristics and readmission rates for each calendar year. Trends of inpatient mortality, mean length of hospital stay (LOS) and mean total hospital cost (THC) were calculated using a multivariate logistic trend analysis adjusting for age, gender, insurance status, comorbidity burden and hospital factors. Furthermore, trends between CD and UC readmissions were compared using regression of the interaction coefficient after adjusting for age and gender to determine relative trends between the two populations. Stata^® Version 16 software (StataCorp, TX, United States) was used for statistical analysis and P value ≤ 0.05 were considered statistically significant.

Results: Total number of 30 d readmissions increased from 6202 in 2010 to 7672 in 2018 for CD and from 3272 in 2010 to 4234 in 2018 for UC. We noted increasing trends for 30-day all-cause readmission rate of CD from 14.9% in 2010 to 17.6% in 2018 (P-trend < 0.001), CD specific readmission rate from 7.1% in 2010 to 8.2% in 2018 (P-trend < 0.001), 30-day all-cause readmission rate of UC from 14.1% in 2010 to 15.7% in 2018 (P-trend = 0.003), and UC specific readmission rate from 5.2% in 2010 to 5.6% in 2018 (P-trend = 0.029). There was no change in the risk adjusted trends of inpatient mortality and mean LOS for CD and UC readmissions. However, we found an increasing trend of mean THC for UC readmissions. After comparison, there was no statistical difference in the trends for 30 d all-cause readmission rate, inpatient mortality, and mean LOS between CD and UC readmissions.

Conclusion: There was an increase in total number of 30 d readmissions for CD and UC with a trend towards increasing 30 d all-cause readmission rates.

Background: Vibration-controlled transient elastography (VCTE) is proposed as a second step of examination to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) after triaging by the fibrosis-4 (FIB-4) index. Recently, VCTE-based scoring systems, including FibroScan-AST (FAST), Agile 3+, and Agile 4, emerged to determine the status of NAFLD. However, the significance of these scoring systems remains unknown in narrowing the high-risk group of NAFLD patients with comorbidities, including hepatocellular carcinoma (HCC) and esophagogastric varices (EGV).

Aim: To clarify the significance of VCTE-based scoring systems to narrow the high-risk group of NAFLD patients with comorbidities.

Methods: We performed a cross-sectional study to investigate the usefulness of VCTE-based scoring systems and other fibrosis markers to narrow the high-risk group of patients with NAFLD. FIB-4 index was used for the first triage. Risk groups of FAST, Agile 3+, and Agile 4 were stratified according to the published data. Among the 191 patients with NAFLD, there were 26 (14%) and 25 patients (13%) with HCC and EGV, respectively.

Results: When 1.3 was used as a cutoff value, the FIB-4 index narrowed the risk group to 120 patients, in which all patients with HCC and/or EGV were included. High risk group of Agile 3+ could subsequently narrow the risk group. The prevalence of HCC and EGV at this step were 33% (26/80) and 31% (25/80), respectively. In further narrowing of EGV, Agile 4 aggregated the patients with EGV into 43 patients, of whom 23 (53%) had EGV. FAST failed to narrow the risk group of patients with comorbidities. When 2.6 was used as a cutoff value of the FIB-4 index, three patients with HCC and two patients with EGV were missed at the first triage.

Conclusion: Agile 3+ and Agile 4 are useful to narrow the NAFLD patient group, in which patients may have HCC and/or EGV.

Hepatocellular carcinoma (HCC) is the second cause of cancer-related mortality. The diagnosis of HCC depends mainly on -fetoprotein, which is limited in its diagnostic and screening capabilities. There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment. New targets of therapy could enhance survival and create future alternative curative methods. In silico analysis provides both; discovery of biomarkers, and understanding of the molecular pathways, to pave the way for treatment development. This review discusses the role of in silico analysis in the discovery of biomarkers, molecular pathways, and the role the author has contributed to this area of research. It also discusses future aspirations and current limitations. A literature review was conducted on the topic using various databases (PubMed, Science Direct, and Wiley Online Library), searching in various reviews, and editorials on the topic, with overviewing the author's own published and unpublished work. This review discussed the steps of the validation process from in silico analysis to in vivo validation, to incorporation into clinical practice guidelines. In addition, reviewing the recent lines of research of bioinformatic studies related to HCC. In conclusion, the genetic, molecular and epigenetic markers discoveries are hot areas for HCC research. Bioinformatics will enhance our ability to accomplish this understanding in the near future. We face certain limitations that we need to overcome.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract, mostly from the stomach. GISTs are derived from the myenteric interstitial cells of Cajal and are caused by several mutations in the c-kit and platelet-derived growth factor receptor genes. Clinically, GISTs are detected by endoscopic and imaging findings and are diagnosed by immunostaining. Surgery is the first line of treatment, and if the tumor is relatively small, minimally invasive surgery such as laparoscopy is performed. In recent years, neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs. Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs. It is important to assess the risk of recurrence after GIST resection. However, the effect of tyrosine kinase inhibitor use will vary by the mutation of c-kit genes and the site of mutation. Furthermore, information regarding gene mutation is indispensable when considering the treatment policy for recurrent GISTs. This article reviews the clinicopathological characteristics of GISTs along with the minimally invasive and multidisciplinary treatment options available for these tumors. The future perspectives for diagnostic and treatment approaches for these tumors have also been discussed.

Background: Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Eradication rates have fallen, mainly due to antimicrobial resistance. Consensus guidelines recommend that first-line treatment is based on the local prevalence of antimicrobial resistance and that rescue therapies are guided by antimicrobial susceptibility testing (AST). However, H. pylori culture is challenging and culture-based AST is not routinely performed in the majority of hospitals. Optimisation of H. pylori culture from clinical specimens will enable more widespread AST to determine the most appropriate antimicrobials for H. pylori eradication.

Aim: To determine whether dual antrum and corpus biopsy sampling is superior to single antrum biopsy sampling for H. pylori culture.

Methods: The study received ethical approval from the joint research ethics committee of Tallaght University Hospital and St. James's Hospital. Patients referred for upper gastrointestinal endoscopy were invited to participate. Biopsies were collected in tubes containing Dent's transport medium and patient demographics were recorded. Biopsies were used to inoculate Colombia blood agar plates. Plates were incubated under microaerobic conditions and evaluated for the presence of H. pylori. Statistical analyses were performed using Graphpad PRISM. Continuous variables were compared using the two-tailed independent t-test. Categorical variables were compared using the two-tailed Fisher exact test. In all cases, a P value less than 0.05 was considered significant.

Results: In all, samples from 219 H. pylori-infected patients were analysed in the study. The mean age of recruited patients was 48 ± 14.9 years and 50.7% (n = 111) were male. The most common endoscopic finding was gastritis (58.9%; n = 129). Gastric ulcer was diagnosed in 4.6% (n = 10) of patients, while duodenal ulcer was diagnosed in 2.7% (n = 6). Single antrum biopsies were collected from 73 patients, whereas combined antrum and corpus biopsies were collected from 146 patients. There was no significant difference in age, sex or endoscopic findings between the two groups. H. pylori was successfully cultured in a significantly higher number of cases when combined antrum and corpus biopsies were used compared to a single antrum biopsy [64.4% (n = 94/146) vs 49.3% (36/73); P = 0.04)].

Conclusion: Combined corpus and antrum biopsy sampling improves H. pylori culture success compared to single antrum biopsy sampling.

Background: Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer (CRC), with heightened risk for younger population. Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria. However, those fail in term of applicability.

Aim: To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor. Further, the study also aims to examine the association of risk factors to the CRC heredity.

Methods: The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease's risk factors. Data were analyzed through Chi-Square, Fischer exact, t-test, Mann-Whitney, and multiple logistics.

Results: There are significant differences of MSH2 within CRC group among tissue and blood; yet, negative for significance between groups. Through the blood gene expression fifth percentile, the hereditary CRC cut-off is 11059 fc, dividing the 40 CRC respondents to 32.5% with hereditary CRC. Significant risk factors include age, family history, and staging. Nonetheless, after multivariate control, age is just a confounder. Further, the study develops a probability equation with area under the curve 82.2%.

Conclusion: Numerous factors have significant relations to heredity of CRC patients. However, true important factors are staging and family history, while age and others are confounders. The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression, 11059 fc. These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.

Bacteria of the human intestinal microflora have a dual role. They promote digestion and are part of a defense mechanism against pathogens. These bacteria could become potential pathogens under certain circumstances. The term "bacterial translocation" describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. In some cases, the passage of bacteria and endotoxins could result in blood stream infections and in multiple organ failure. Open elective abdominal surgery more frequently results in malfunction of the intestinal barrier and subsequent bacterial translocation and blood stream infections than laparoscopic surgery. Postoperative sepsis is a common finding in patients who have undergone non-elective abdominal surgeries, including trauma patients treated with laparotomy. Postoperative sepsis is an emerging issue, as it changes the treatment plan in surgical patients and prolongs hospital stay. The association between bacterial translocation and postoperative sepsis could provide novel treatment options.

Background: Acute pancreatitis (AP) is an inflammatory disease, which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal. The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely, mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP). Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial.

Aim: To identify the role of the chemokine receptor 8 (CCR8), expressed by T-helper type-2 Lymphocytes and peritoneal macrophages, and its possible association to Interleukin (IL)-6 and AP stratification.

Methods: This study was a prospective case-control study. A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital. Bioassays were performed on 29 patients (14 MAP, 11 MSAP, and 4 SAP) and 6 healthy controls as part of a preliminary study. A total of 12 mL of blood samples were collected at Day (D) 1, 3, 5, and 7 post epigastric pain. Using multiplex immunoassay panels, real-time polymerase chain reaction (qRT-PCR) arrays, and multicolour flow cytometry analysis, immune response-related proteins, genes, and cells were profiled respectively. GraphPad Prism™ software and fold change (FC) analysis was used to determine differences between the groups. P<0.05 was considered significant.

Results: The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P = 0.001 and P = 0.013 respectively, in a multiplex assay. When a FC of 2 was applied to identify differentially expressed genes using RT² Profiler, CCR8 was shown to increase steadily with disease severity from MAP (1.33), MSAP (38.28) to SAP (1172.45) median FC. Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log₁₀, compared to healthy control respectively at D3. The findings also showed differing lymphocyte and monocyte cell frequency between the groups. With monocyte population frequency as high as 70% in MSAP at D3.

Conclusion: The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.

Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.