Canadian Journal of Gastroenterology and Hepatology最新文献

Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12-250 months). All cardiovascular events were carefully recorded and detailed in the patients' charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60-6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36-7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.

Purpose: Our objective was to compare the value of positron emission tomography/magnetic resonance imaging (PET/MRI) with the new imaging agent [⁶⁸Ga]Ga-DOTA-FAPI-04 and the traditional imaging agent [¹⁸F]FDG for the preoperative diagnosis of gastric cancer.

Methods: Forty patients with gastric cancer diagnosed by gastroscopy in gastrointestinal surgery at our hospital from June 2020 to January 2021 were analyzed. All patients underwent simultaneous [⁶⁸Ga]Ga-DOTA-FAPI-04 and [¹⁸F]FDG PET/MRI. The standard uptake value (SUV), fat removal standard uptake value (SUL), and diagnostic sensitivity, specificity, and accuracy for primary and metastatic lesions were compared, and their diagnostic value for different lymph node dissection stages was analyzed.

Results: The median age of the patients in this cohort was 68 years. Twenty-nine patients underwent surgery, and 11 patients underwent gastroscopic biopsy. The SUV_max of primary lesions in the FDG group and the FAPI group was 5.74 ± 5.09 and 8.06 ± 4.88, respectively (P < 0.01); SUL_max values were 3.52 ± 2.80 and 5.64 ± 3.25, respectively (P < 0.01). The SUV_max of metastases in the two groups was 3.81 ± 3.08 and 5.17 ± 2.80, respectively (P < 0.05). The diagnostic sensitivities for primary lesions in the FDG group and the FAPI group were 0.72 and 0.94, respectively (P < 0.05). Combined with postoperative pathological staging, there was no difference in diagnostic sensitivity and specificity of lymph node staging between the FDG and FAPI groups (P > 0.05).

Conclusion: Compared with the traditional imaging agent, [⁶⁸Ga]Ga-DOTA-FAPI-04 has better diagnostic efficiency but no substantial advantage for preoperative lymph node staging.

Purpose: The purpose of the current study was to determine whether there is a difference between high levels of microsatellite instability (MSI-H) and microsatellite stability (MSS) in DNA mismatch repair-deficient (DMMR) colorectal cancer (CRC) patients.

Methods: A total of 452 CRC patients with DMMR from December, 2014, to April, 2021, in our hospital were selected retrospectively. However, only 105 patients underwent Sanger or next-generation-sequencing (NGS) to confirm their microsatellite status. Ultimately, 55 MSI-H patients and 20 MSS patients with intact medical record information were included in this study.

Results: The MSS group was associated with a higher mutation rate in the KRAS gene (P=0.011). Meanwhile, MSI-H was related to colon cancer (P < 0.01). However, no significant differences in other clinical characteristics were observed between the two groups of patients. There was no significant difference between the MSI-H and MSS groups in terms of overall survival (OS) (P=0.398) and disease-free survival (DFS) (P=0.307).

Conclusion: The MSI-H status was associated with colon cancer and a lower mutation rate of the KRAS gene in DMMR patients. In CRC-DMMR patients, the MSS group exhibited better OS and DFS than the MSI-H group, although these differences were not statistically significant. Accordingly, in clinical practice, we should not confuse these two types of patients.

Background: The serum systemic inflammation biomarkers are known predictors of colorectal cancer (CRC) patient prognosis. However, their significance in human immunodeficiency virus (HIV)-infected patients with CRC has not been studied. To address this gap, we conducted a retrospective study to evaluate the prognostic value of preoperative systemic inflammation biomarkers in HIV-infected patients with CRC.

Methods: The study enrolled 57 patients with colorectal cancer (CRC) and HIV who underwent surgery at the Shanghai Public Health Clinical Center between January 2015 and December 2021. Preoperative tests were conducted, and systemic inflammation biomarkers were measured. The patients were categorized into two groups using the optimal cut-off value. The Kaplan-Meier method and the log-rank test were used to determine overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional regression model. A time-dependent receiver operating characteristic (t-ROC) was used to compare the prognostic abilities of the biomarkers.

Results: The study included 57 HIV-infected CRC patients, with a median age of 60 and a follow-up time ranging from 3 to 86 months. Of the patients, 49 were male and 8 were female. The cumulative three-year OS and PFS rates were 55.0% and 45.0%, respectively. The optimal cut-off value for preoperative NLR was found to be 2.8, which was significantly correlated with lower CD8+ T and CD3+ T lymphocyte counts. Multivariate Cox regression analysis revealed that a low NLR was an independent predictor of better OS and PFS (OS: HR = 0.094, 95% CI: 0.02-0.45, P=0.003; PFS: HR = 0.265, 95% CI: 0.088-0.8, P=0.019). The time-dependent receiver operating characteristic (t-ROC) analysis showed that NLR was a superior systemic inflammation biomarker for predicting the prognosis of HIV-infected CRC patients throughout the observation period.

Conclusion: The preoperative neutrophil-to-lymphocyte ratio (NLR), an easily measurable immune biomarker, may provide useful prognostic information in HIV-infected colorectal cancer (CRC) patients.

Background: Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking.

Objectives: To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease.

Methods: Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age).

Results: TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides.

Conclusion: Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

Following the SARS-CoV-2 outbreak and the subsequent development of the COVID-19 pandemic, organs such as the lungs, kidneys, liver, heart, and brain have been identified as priority organs. Liver diseases are considered a risk factor for high mortality from the COVID-19 pandemic. Besides, liver damage has been demonstrated in a substantial proportion of patients with COVID-19, especially those with severe clinical symptoms. Furthermore, antiviral medications, immunosuppressive drugs after liver transplantation, pre-existing hepatic diseases, and chronic liver diseases such as cirrhosis have also been implicated in SARS-CoV-2-induced liver injury. As a result, some precautions have been taken to prevent, monitor the virus, and avoid immunocompromised and susceptible individuals, such as liver and kidney transplant recipients, from being infected with SARS-CoV-2, thereby avoiding an increase in mortality. The purpose of this review was to examine the impairment caused by SARS-CoV-2 infection and the impact of drugs used during the pandemic on the mortality range and therefore the possibility of preventive measures in patients with liver disease.

Background: Nucleotide analogues (NTs) monotherapy may have a more significant effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with PEGylated interferon α (PegIFNα). Therefore, this study aimed to explore whether NTs have more significant antiviral effects than NSs in combination therapy with PegIFNα.

Methods: Chronic hepatitis B (CHB) patients treated with PegIFNα plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction >1 log₁₀ IU/mL after 48 weeks were analyzed.

Results: A total of 95 patients were included and divided into the PegIFNα + NTs group and the PegIFNα + NSs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (-3.52 vs. -2.33 log₁₀ IU/mL, P=0.032) and a higher proportion of patients with HBsAg reduction >1 log₁₀ IU/mL (100.0% vs. 72.2%, P=0.003) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the "add-on" subgroups. PegIFNα plus NTs (OR = 36.667, 95% CI = 3.837-350.384) was an independent predictor for HBsAg reduction >1 log₁₀ IU/mL after 48 weeks.

Conclusion: This study suggests that PegIFNα plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and "add-on" patients.

Objective: Gastroesophageal adenocarcinoma (GEA) is a high deadly and heterogeneous cancer. RNA N6-methyladenosine (m⁶A) modification plays a non-negligible role in shaping individual tumour microenvironment (TME) characterizations. However, the landscape and relationship of m⁶A modification patterns and TME cell infiltration features remain unknown in GEA.

Methods: In this study, we examined the TME of GEA using assessments of the RNA-sequencing data focusing on the distinct m⁶A modification patterns from the public databases. Intrinsic patterns of m⁶A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumour immune cell infiltration, oncological outcomes, and treatment responses. The expression of key m⁶A regulators and module genes was validated by qRT-PCR analysis.

Results: We identified two distinct m⁶A modification patterns of GEA (cluster 1/2 subgroup), and correlated two subgroups with TME cell-infiltrating characteristics. Cluster 2 subgroup correlates with a poorer prognosis, downregulated PD-1 expression, higher risk scores, and distinct immune cell infiltration. In addition, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. COL4A1 and COL5A2 in the brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Finally, a prognostic risk score was constructed using m⁶A regulator-associated signatures that represented an independent prognosis factor for GEA. Interestingly, COL5A2 expression was linked to the response to anti-PD-1 immunotherapy, m⁶A regulator expression, and risk score.

Conclusion: Our work identified m⁶A RNA methylation regulators as an important class of players in the malignant progression of GEA and were associated with the complexity of the TME. COL5A2 may be the potential biomarker which contributes to predicting the response to anti-PD-1 immunotherapy and patients' prognosis.

Aim: The aim of this study is to identify cuproptosis-related lncRNAs and construct a prognostic model for pancreatic cancer patients for clinical use.

Methods: The expression profile of lncRNAs was downloaded from The Cancer Genome Atlas database, and cuproptosis-related lncRNAs were identified. The prognostic cuproptosis-related lncRNAs were obtained and used to establish and validate a prognostic risk score model in pancreatic cancer.

Results: In total, 181 cuproptosis-related lncRNAs were obtained. The prognostic risk score model was constructed based on five lncRNAs (AC025257.1, TRAM2-AS1, AC091057.1, LINC01963, and MALAT1). Patients were assigned to two groups according to the median risk score. Kaplan-Meier survival curves showed that the difference in the prognosis between the high- and low-risk groups was statistically significant. Multivariate Cox analysis showed that our risk score was an independent risk factor for pancreatic cancer patients. Receiver operator characteristic curves revealed that the cuproptosis-related lncRNA model can effectively predict the prognosis of pancreatic cancer. The principal component analysis showed a difference between the high- and low-risk groups intuitively. Functional enrichment analysis showed that different genes were involved in cancer-related pathways in patients in the high- and low-risk groups.

Conclusion: The risk model based on five prognostic cuproptosis-related lncRNAs can well predict the prognosis of pancreatic cancer patients. Cuproptosis-related lncRNAs could be potential biomarkers for pancreatic cancer diagnosis and treatment.