Canadian Journal of Gastroenterology and Hepatology最新文献

Background: H2.0-like homeobox (HLX) is highly expressed in several hematopoietic malignancies. However, the role of HLX in the carcinogenesis and progression of colorectal cancer (CRC) patients has rarely been reported.

Methods: In this study, the data were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The diagnostic value of HLX was analyzed by the R package "pROC." The overall survival was estimated using the "survival" and "survminer" packages. A nomogram was established to predict 1-, 3-, and 5-year overall survival of CRC patients. The CIBERSORT software was employed to calculate the relative proportions of 22 immune cells.

Results: HLX expression was downregulated in CRC patients. Remarkably, HLX expression was increased with stage (stage I-stage III) of CRC, and the CRC patients with high HLX expression exhibited a poor prognosis. The promoter methylation level of HLX was prominently increased in CRC samples compared to paracancerous samples. We also found that the six miRNAs target HLX genes, leading to its downregulation, and HLX expression had a negative correlation with its downstream target gene BRI3BP in both CRC and normal samples. Finally, we found that the 12 immune infiltrating cells were observably different between high and low HLX expression groups. The HLX had a significant positive correlation with 8 immune checkpoints (PD-1 (PDCD1), CTLA4, PDL-1 (CD274), PDL-2 (PDCD1LG2), CD80, CD86, LAG3, and TIGIT) expressions.

Conclusion: HLX probably played a carcinostasis role in the early stages of CRC but exhibited a cancer-promoting effect in the advanced stages. Meanwhile, HLX could serve as a reliable prognostic indicator for CRC.

Bleeding after endoscopic sphincterotomy (ES) remains as a major challenge during ERCP procedure. Standard endoscopic haemostatic procedures have demonstrated good performance for bleeding control. Novel endoscopic haemostatic agents have also been widely used in gastrointestinal bleeding management. Regardless, there is still a paucity of high-quality evidence evaluating the practicality of these agents in ERCP. This case series study was performed on the patients who underwent ERCP procedure in a tertiary referral private hospital within 2 years period. Post-ES immediate bleeding is defined as the onset of bleeding at the time of sphincterotomy. Treatment groups for post-ES bleeding are divided into (1) standard haemostatic methods and (2) novel haemostatic agents. There were 40 patients who received standard haemostatic treatment and 60 patients who received novel haemostatic agents. Initial haemostasis was achieved in all patients. Two patients who received standard haemostatic treatment had rebleeding. Meanwhile, no patients in novel haemostatic treatment group had rebleeding. In conclusion, novel haemostatic agent can be considered as an easy and practical method in daily practice, especially when an ERCP procedure is performed. Further studies with larger sample size which, if possible, can also include a cost-effectiveness analysis are still required to implement these agents as a standard procedure in clinical practice. (This abstract has been presented at the American College of Gastroenterology meeting October 2021).

Methods: Transcriptome data and clinical data of HCC were downloaded from the TCGA database. Screen important genes based on the random forest method, combined with differential expression genes (DEGs) to screen out important DEGs. The Kaplan‒Meier curve was used to evaluate its prognostic significance. Cox regression analysis was used to construct a survival prognosis prediction model, and the ROC curve was used to verify it. Finally, the mechanism of action was explored through GO and KEGG pathway enrichment and GeneMANIA coexpression analyses.

Results: Seven important DEGs were identified, three were highly expressed and four were lowly expressed. Among them, GPRIN1, MYBL2, and GSTM5 were closely related to prognosis (P < 0.05). After the survival prognosis prediction model was established, the survival analysis showed that the survival time of the high-risk group was significantly shortened (P < 0.001), but the ROC analysis indicated that the model was not superior to staging. Twenty coexpressed genes were screened, and enrichment analysis indicated that glutathione metabolism was an important mechanism for these genes to regulate HCC progression.

Conclusion: This study revealed the important DEGs affecting HCC progression and provided references for clinical assessment of patient prognosis and exploration of HCC progression mechanisms through the construction of predictive models and gene enrichment analysis.

Objectives: The rapidly evolving organ failure and high short-run mortality of acute-on-chronic liver failure (ACLF) are inseparable from the role of systemic inflammatory response. S100A8 and S100A9 are associated with the excessive cytokine storm and play a decisive part within the process of inflammation. We aimed to clarify the role of them in predicting prognosis of hepatitis B virus-related ACLF (HBV-ACLF).

Methods: S100A8 and S100A9 levels were analyzed in plasma of 187 transplant-free HBV-ACLF patients, 28 healthy controls and 40 chronic hepatitis B (CHB) patients. S100A8 and S100A9 mRNAs were checked in liver samples from 32 HBV-ACLF patients with liver transplantation, 19 patients undergoing surgery for hepatic hemangioma and 10 CHB patients with needle biopsy.

Results: The plasma levels of the S100A8 and S100A9 were higher in HBV-ACLF patients than in CHB patients (S100A8 : P < 0.001 and S100A9 : P < 0.001) and healthy controls (S100A8 : P < 0.001 and S100A9 : P < 0.001), and similar results were obtained for mRNA expression. Moreover, both proteins were related to ACLF grade, different types of organ failure, and infection, and they correlated with other prognostic scoring systems. S100A8 and S100A9 can dependently predict 28/90-day mortality (28-day: S100A8: hazard ratio (HR): 1.027; 95% confidence interval (CI): 1.007-1.048; P=0.026, S100A9 : HR: 1.009; 95% CI: 1.001-1.017; P=0.007, 90-day: S100A8 : HR: 1.023; 95% CI: 1.011-1.035; P=0.004, S100A9 : HR: 1.008; 95% CI: 1.004-1.012; and P < 0.001). Among all of the scoring systems, the combined scoring model (S100A8 and S100A9 jointly with the Chronic Liver Failure-Consortium Organ Failure score (CLIF-C OFs)) displayed the highest area under the receiver operating curve (0.923 (95% CI, 0.887-0.961)) in the prediction of 90-day mortality.

Conclusions: S100A8 and S100A9 are promising biomarkers for the analysis of risk stratification and prognosis in ACLF patients. In addition, combining them with the CLIF-C OFs may better predict the prognosis of ACLF.

Background and aims: Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) have become increasingly recognized, both of which affect human health globally. The association of H. pylori infection with NAFLD remains unclear.

Methods: PubMed, EMBASE, and Cochrane Library databases were searched. Only a random-effects model was used. Odds ratios (ORs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for the combined estimates of raw data. Adjusted ORs (aORs) and hazard ratios (aHRs) with 95% CIs were calculated for the combined estimates of data adjusted for confounders.

Results: Thirty-four studies with 218573 participants were included. Based on unadjusted data from 26 cross-sectional studies and 3 case-control studies, H. pylori infection was significantly associated with the presence of NAFLD (OR = 1.26, 95% CI = 1.17-1.36, P < 0.001). Based on adjusted data from 15 cross-sectional studies and 1 case-control study, H. pylori infection was significantly associated with the presence of NAFLD (aOR = 1.25, 95% CI = 1.08-1.44, P < 0.001). Compared with control subjects without NAFLD, patients with moderate (OR = 1.67, 95% CI = 1.17-2.39, P = 0.005) and severe (OR = 1.71, 95% CI = 1.30-2.24, P < 0.001) NAFLD, but not those with mild NAFLD (OR = 1.14, 95% CI = 0.9-1.45, P = 0.286), had significantly higher proportions of H. pylori infection. The association of H. pylori infection with the occurrence of NAFLD was statistically significant based on adjusted data from 3 cohort studies (aHR = 1.18, 95% CI = 1.05-1.34, P = 0.007), but not based on unadjusted data from 3 cohort studies (RR = 1.41, 95% CI = 0.80-2.48, P = 0.237).

Conclusion: H. pylori infection is associated with NAFLD, especially moderate and severe NAFLD. The impact of H. pylori eradication on the prevention of NAFLD should be further explored.

Gambogic acid (GA) is a natural xanthonoid secreted by Garcinia hanburyi tree. It possesses anti-cancer activity in various types of cancers. In gastric cancer, it inhibits cell proliferation through increasing apoptosis. However, whether necroptosis is involved in the GA-induced proliferation inhibited in gastric cancer is unknown. In the present study, we found that RIPK1 specific inhibitor necrostatin-1 (Nec-1) attenuated GA-induced proliferation inhibition. GA treatment increased the phosphorylation of necroptosis-related proteins, RIPK1, RIPK3, and MLKL, and their interactions to form the necrosome complex. The effector protein Drp-1 was dephosphorylated by GA treatment. Inhibition of necroptosis by different inhibitors and PGAM5 knockdown attenuated GA-induced cell death in gastric cancer cell lines, thereby attenuating GA-caused cell proliferation inhibition. All the data supported the conclusion that GA could inhibit gastric cancer cell proliferation by inducing necroptosis.

Purpose: The current study was designed to investigate the impact of blood urea nitrogen (BUN), serum uric acid (UA), and cystatin (CysC) on the short-term outcomes and prognosis of colorectal cancer (CRC) patients undergoing radical surgery.

Methods: CRC patients who underwent radical resection were included from Jan 2011 to Jan 2020 in a single clinical centre. The short-term outcomes, overall survival (OS), and disease-free survival (DFS) were compared in different groups. A Cox regression analysis was conducted to identify independent risk factors for OS and DFS.

Results: A total of 2047 CRC patients who underwent radical resection were included in the current study. Patients in the abnormal BUN group had a longer hospital stay (p=0.002) and more overall complications (p=0.001) than that of the normal BUN group. The abnormal CysC group had longer hospital stay (p < 0.01), more overall complications (p=p < 0.01), and more major complications (p=0.001) than the normal CysC group. Abnormal CysC was associated with worse OS and DFS for CRC patients in tumor stage I (p < 0.01). In Cox regression analysis, age (p < 0.01, HR = 1.041, 95% CI = 1.029-1.053), tumor stage (p < 0.01, HR = 2.134, 95% CI = 1.828-2.491), and overall complications (p=0.002, HR = 1.499, 95% CI = 1.166-1.928) were independent risk factors for OS. Similarly, age (p < 0.01, HR = 1.026, 95% CI = 1.016-1.037), tumor stage (p < 0.01, HR = 2.053, 95% CI = 1.788-2.357), and overall complications (p=0.002, HR = 1.440, 95% CI = 1.144-1.814) were independent risk factors for DFS.

Conclusion: In conclusion, abnormal CysC was significantly associated with worse OS and DFS at TNM stage I, and abnormal CysC and BUN were related to more postoperative complications. However, preoperative BUN and UA in the serum might not affect OS and DFS for CRC patients who underwent radical resection.

Background: The drug-eluting beads transarterial chemoembolization (DEB-TACE) has already been used in hepatic malignancies. We aim to evaluate the efficacy and safety of DEB-TACE in treating primary or secondary liver cancer.

Methods: We retrospectively evaluated 59 patients with hepatic malignancies, including 41 patients with primary liver cancer and 18 patients with secondary liver cancer, between September 2016 and February 2019. All patients were treated with DEB-TACE. Objective response rate (ORR) and disease control rate (DCR) were evaluated by mRECIST. The pain was assessed using a numerical rating scale (NRS) where 0 represented no pain, and a score of ten was unbearable. Adverse reactions were assessed according to Common Terminology Criteria for Adverse Events 4.0 (CTCAE4.0).

Results: In the subgroup of primary liver cancer, 3 patients (7.32%) got complete response, 13 patients (31.71%) got partial response, 21 patients (51.22%) experienced stable disease, and 4 patients (9.76%) suffered progressive disease; ORR was 39.02% and DCR was 90.24%. In the subgroup of secondary liver cancer, 0 patients (0%) got complete response, 6 patients (33.33%) got partial response, 11 patients (61.11%) experienced stable disease, and 1 patient (5.56%) suffered progressive disease; ORR was 33.33% and DCR was 94.44%. We did not find any difference when comparing the efficacy between primary and secondary liver cancer (P=0.612). The one-year survival rate was 70.73% for primary liver cancer and 61.11% for secondary liver cancer. There was no significant difference between the two groups (P=0.52). For the patients with CR or PR, no factor could predict the efficacy of DEB-TACE. The most common treatment-related adverse reactions were short-term liver function disorders. The symptoms included fever (20.34%), abdomen pain (16.95%), and vomiting (5.08%), all patients with adverse reactions got remission after treatment.

Conclusions: DEB-TACE has a promising effect in the treatment of primary or secondary liver cancer. The treatment-related adverse reactions are tolerable.

Background: The surgical treatment of primary intrahepatic bile duct stones is associated with high rates of postoperative complications, stone recurrence, and reoperation. This study aimed to report an 11-year experience in the management of postoperative recurrence of intrahepatic bile duct stones, analyze the causes of the reoperation, and establish appropriate surgical procedures.

Materials and methods: The records of 148 patients with postoperative recurrence of primary intrahepatic bile duct stones treated from January 2005 to December 2015 were retrospectively reviewed. Prior surgical treatment and postoperative data were analyzed to investigate possible causes of recurrence and reoperation.

Results: All patients with a prior cholangiojejunostomy (n = 61) developed biliary stenosis (100%). Of the 86 patients without cholangiojejunostomy, 71 (82.56%) had abnormalities in the structure and function of the lower end of the common bile duct, and 86 had hilar and intrahepatic bile duct stenosis. Of all 148 patients, 136 (91.89%) had positive intraoperative bile cultures. Patients were treated with a modified surgical procedure, and the combined excellent and good rate of long-term outcomes reached 85.48% (106/124). The stone recurrence rate of the 124 patients decreased from 100% (124/124) of the prior operation to 5.65% (7/124) during the reoperation.

Conclusions: The pathogenesis of primary intrahepatic bile duct stones is associated with biliary infection and intrahepatic bile duct cholestasis. According to the etiology and pathogenic mechanism, surgical procedures that improve long-term outcomes and reduce postoperative recurrence include bile duct exploration with stone extraction, partial hepatectomy, hilar ductoplasty, and Roux-en-Y hepaticojejunostomy.

Background: The impact of indication for pediatric liver transplantation on waitlist and post-transplant mortality outcomes is well known, but the impact on intent-to-treat outcomes has not been investigated. Intent-to-treat survival analysis is important in this study because it is more comprehensive, combining the transplant outcomes of waitlist mortality, post-transplant mortality, and transplant rate into a single metric to elucidate any disparities in outcomes based on indication.

Methods: Cox regression was used to analyze factors impacting survival in 8,002 children listed for liver transplant in the UNOS database between 2006 and 2016. The Kaplan-Meier method and log-rank test were used to assess differences in waitlist, post-transplant, and intent-to-treat mortality among the top 5 indications of biliary atresia, acute hepatic necrosis, metabolic disorders, hepatoblastoma, and autoimmune cirrhosis.

Results: When compared to the reference group of biliary atresia, multivariate analyses showed that every indication was associated with inferior intent-to-treat outcomes except for metabolic disorders. Hepatoblastoma (hazard ratio (HR): 3.73), autoimmune cirrhosis (HR: 1.86), and AHN (HR: 1.77) were associated with significantly increased intent-to-treat mortality. Hepatoblastoma was also associated with increased post-transplant mortality (HR: 3.77) and was the only indication significantly associated with increased waitlist mortality (HR: 6.43).

Conclusion: Significant disparity exists across all indications with respect to an increased intent-to-treat mortality, along with an increased post-transplant and waitlist mortality, when compared to the biliary atresia reference group. If further studies validate these findings, a reexamination of the equitable distribution of allografts for transplant may be warranted as well as a focus on disparities in survival after transplant.