Canadian Journal of Gastroenterology and Hepatology最新文献

Objectives: Although raltitrexed shows therapeutic effects in many types of malignant tumors, the therapeutic effects and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) loaded with raltitrexed for the treatment of hepatocellular carcinoma (HCC) are rare. This study aimed to investigate the safety and efficacy of DEB-TACE with raltitrexed-loaded CalliSpheres beads (CB) in patients with unresectable or recurrent HCC.

Methods: Between May 2018 and October 2021, 41 patients with unresectable or recurrent HCC treated by DEB-TACE loaded with raltitrexed were retrospectively enrolled. The primary end points were overall survival and progression-free survival. The response evaluation criteria in solid tumors (RECIST) criteria and modified RECIST criteria (mRECIST) were used to assess the tumor response after the DEB-TACE procedure.

Results: A total of 79 DEB-TACE procedures were successfully performed, and the technical success rate was 100%. The overall response rate and disease control rate assessed by mRECIST criteria were 76.9% and 88.5%, 62.5% and 70.8%, and 35.3% and 47.1%, respectively, at 1, 3, and 6 months postprocedure. The mean progression-free survival and overall survival were 21.6 ± 3.6 and 43.7 ± 5.8 months, respectively. The 6-, 24-, and 36-month overall survival rates were 86.8%, 62.7%, and 57.1%, respectively. Minor complications were observed in 21 patients (51.2%), with no treatment-related mortality or severe adverse events. The most common treatment-related complications were abdominal pain (48.8%) and nausea (29.3%).

Conclusion: DEB-TACE with raltitrexed-loaded CB suggests a feasible, safe, and efficacious palliative regimen in unresectable or recurrent HCC patients.

Aim: This study compared the efficacy and safety of endoscopic submucosal dissection (ESD) combined with clip-and-snare method and a prelooping technique (CSM-PLT) with ESD alone for the treatment of gastric submucosal tumors (gSMTs).

Methods: We retrospectively enrolled a matched group of 86 patients who received ESD combined with CSM-PLT or ESD alone from July 2010 to July 2020. The primary outcomes included complete resection, en bloc resection, and R0 resection.

Results: Eighty-six patients with gSMTs were enrolled in ESD combined with CSM-PLT group and ESD group, respectively. There were no significant differences in gender, age, tumor size, tumor location, and tumor origin between the two groups. The complete resection, en bloc resection, and R0 resection rates were comparable between two groups (P=1, P=0.31, and P=0.25, respectively). There were no significant differences in terms of hospital stays, hospitalization cost, postoperative complications, and residual rate (P=0.42, P=0.74, P=0.65, and P=1, respectively) between the two groups. However, the ESD combined with CSM-PLT was associated with a shorter procedure duration and fewer intraoperative complications (P < 0.001 and P=0.024, respectively). In addition, the incidence of intraoperative bleeding in ESD combined with CSM-PLT group was significantly lower than that in ESD group (P=0.04).

Conclusion: Both ESD combined with CSM-PLT and ESD were effective and safe modalities for the treatment of gSMTs. However, ESD combined with CSM-PLT was associated with a shorter procedure duration and fewer intraoperative complications.

Delta-shaped gastroduodenostomy (DSGD) and overlap gastroduodenostomy (OGD) are the two most widely used intracorporeal Billroth I anastomosis methods after distal gastrectomy. In this study, we compared the short-term outcomes of DSGD and OGD in total laparoscopic distal gastrectomy (TLDG). In a retrospective cohort study, we examined 92 gastric cancer patients who underwent TLDG performed by the same surgeon between January 2014 and June 2018. All patients underwent Billroth I reconstruction (OGD, n = 45; DSGD, n = 47) and D2 lymph node dissection. We retrospectively reviewed the surgical outcomes, clinical pathological results, and endoscopy results. Laparoscopic surgery was successfully performed in both groups without conversion to open surgery. The demographic and clinical characteristics were similar between the two groups (P > 0.05). There were no significant differences between the two groups in operation time (158.9 ± 13.6 min vs. 158.8 ± 14.8 min, P=0.955), anastomotic time (19.4 ± 3.0 min vs. 18.8 ± 2.9 min, P=0.354), intraoperative blood loss (88.9 ± 25.4 mL vs. 83.7 ± 24.3 mL, P=0.321), number of lymph node dissections (31.0 ± 7.1 vs. 29.2 ± 7.5, P=0.229), length of hospital stay (8.8 ± 2.7 days vs. 9.1 ± 3.0 days, P=0.636), fluid intake time (3.1 ± 0.7 days vs. 3.2 ± 0.7 days, P=0.914), and morbidity of postoperative complications (6.7% [3/45] vs. 10.6% [5/47], P=0.499). Endoscopy performed 6 months postoperatively showed that the residual food (P=0.033), gastritis (P=0.029), and bile (P=0.022) classification score significantly decreased in the OGD group, and there were no significant differences 12 months postoperatively. OGD is a safe and effective reconstruction technique with comparable postoperative surgical outcomes and endoscopy results when compared with those of DSGD.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease and is closely associated with cardiometabolic disorders, being insulin resistance (IR) the common pathogenic mechanism. The triglycerides/glucose (TyG) index and triglycerides/HDL-c (TG/HDL) ratio are markers correlated with IR. We compared the capacity of these two indexes, alongside IR, to detect NAFLD.

Methods: In a cross-sectional cohort study, we examined 263 active military personnel from the Colombian Air Force, aged between 29 and 54 years. Anthropometric measurements and biochemical determinations (glycemia, lipid profile, and insulin) were obtained, and ultrasound studies were performed to evaluate the presence of NAFLD. HOMA-IR index was calculated as (fasting insulin (µIU/mL) × fasting glucose (mmol/L)/22.5), the TyG index as Ln (triglycerides (mg/dL) × fasting glucose (mg/dL)/2), and the TG/HDL ratio as (triglycerides (mg/dL)/HDL-c (mg/dL)).

Results: NAFLD ultrasound criteria were met in 70 individuals (26.6%). Subjects with NAFLD had significantly higher values of HOMA-IR (2.55 ± 1.36 vs. 1.51 ± 0.91), TyG (9.17 ± 0.53 vs. 8.7 ± 0.51), and TG/HDL (6.6 ± 4.54 vs. 3.52 ± 2.32) compared to those without NAFLD (p < 0.001). A TyG cutoff point of 8.92 showed an AUC of 0.731, while cutoff points of 3.83 for TG/HDL and 1.68 for HOMA-IR showed an AUC of 0.766 and 0.781, respectively.

Conclusion: Our study shows that novel and lower-cost markers of IR are useful for detecting NALFD, with a performance comparable to the HOMA-IR index. These markers should be used as the first step when screening patients for NAFLD.

Crohn's disease (CD) is a chronic inflammatory disease with a complex interface of broad factors. There are two main treatments for Chron's disease: biological therapy and nonbiological therapy. Biological agent therapy (e.g., anti-TNF) is the most frequently prescribed treatment; however, it is not universally accessible. In fact, in Brazil, many patients are only given the option of receiving nonbiological therapy. This approach prolongs the subsequent clinical relapse; however, this procedure could be implicated in the immune response and enhance disease severity. Our purpose was to assess the effects of different treatments on CD4⁺ T cells in a cohort of patients with Crohn's disease compared with healthy individuals. To examine the immune status in a Brazilian cohort, we analyzed CD4⁺ T cells, activation status, cytokine production, and Treg cells in blood of Crohn's patients. Patients that underwent biological therapy can recover the percentage of CD4⁺CD73⁺ T cells, decrease the CD4⁺ T cell activation/effector functions, and maintain the peripheral percentage of regulatory T cells. These results show that anti-TNF agents can improve CD4⁺ T cell subsets, thereby inducing Crohn's patients to relapse and remission rates.

Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic liver disease characterized by progressive cholangiocyte and bile duct destruction leading to fibrosis and finally to liver cirrhosis. The presence of disease-specific serological antimitochondrial antibody (AMA) together with elevated alkaline phosphatase (ALP) as a biomarker of cholestasis is sufficient for diagnosis. Ursodeoxycholic acid (UDCA) is the first treatment option for PBC. Up to 40% of patients have an incomplete response to therapy, and over time disease progresses to liver cirrhosis. Several risk scores are proposed for better evaluation of patients before and during treatment to stratify patients at increased risk of disease progression. GLOBE score and UK PBC risk score are used for the evaluation of UDCA treatment and Mayo risk score for transplant-free survival. Liver transplantation (LT) is the only treatment option for end-stage liver disease. More than 10 years after LT, 40% of patients experience recurrence of the disease. A liver biopsy is required to establish rPBC (recurrent primary biliary cholangitis). The only treatment option for rPBC is UDCA, and data show biochemical and clinical improvement, plus potential beneficial effects for use after transplantation for the prevention of rPBC development. Additional studies are required to assess the full impact of rPBC on graft and recipient survival and for treatment options for rPBC.

Background and aims: While endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic tool in primary sclerosing cholangitis (PSC), there is conflicting data on associated adverse events. The aims of this systematic review and meta-analysis are to (1) compare ERCP-related adverse events in patients with and without PSC and (2) determine risk factors for ERCP-related adverse events in PSC.

Methods: Embase, PubMed, and CENTRAL were searched between January 1, 2000, and May 12, 2021. Eligible studies included adults with PSC undergoing ERCP and reported at least one ERCP-related adverse event (cholangitis, pancreatitis, bleeding, and perforation) or an associated risk factor. The risk of bias was assessed with the Newcastle-Ottawa scale and Cochrane Risk of Bias 2. Raw event rates were used to calculate odds ratios (ORs) and then pooled using random-effects models.

Results: Twenty studies met eligibility criteria, of which four were included in a meta-analysis comparing post-ERCP adverse events in patients with PSC (n = 715) to those without PSC (n = 9979). We found a significant threefold increase in the 30-day odds of cholangitis in PSC compared to those without (OR 3.263, 95% CI 1.076-9.896; p=0.037). However, there were no significant differences in post-ERCP pancreatitis (PEP), bleeding, or perforation. Due to limitations in primary data, only risk factors contributing to PEP could be analyzed. Accidental passage of the guidewire into the pancreatic duct (OR 7.444, 95% CI 3.328-16.651; p < 0.001; I ² = 65.0%) and biliary sphincterotomy (OR 4.802, 95% CI 1.916-12.033; p=0.001; I ² = 73.1%) were associated with higher odds of PEP in a second meta-analysis including five studies.

Conclusions: In the context of limited comparative data and heterogeneity, PSC patients undergoing ERCP have higher odds of cholangitis despite the majority receiving antibiotics. Additionally, accidental wire passage and biliary sphincterotomy increased the odds of PEP. Future studies on ERCP-related risks and preventive strategies are needed.

To claim the features of nontumor tissue in gastric cancer patients, especially in those who have undergone gastrectomy, and to identify the molecular subtypes, we collected the immunogenic and hallmark gene sets from gene set enrichment analysis. The activity changes of these gene sets between tumor (375) and nontumor (32) tissues acquired from the Cancer Genome Atlas (TCGA-STAD) were calculated, and the novel molecular subtypes were delineated. Subsequently, prognostic gene sets were determined using least absolute shrinkage and selection operator (lasso) regression prognostic method. In addition, functional analysis was conducted. Totally, three subtypes were constructed in the present study, and there were differences in survival among three groups. Functional analysis showed genes from normal gene set were related to cell adhesion, and genes from tumor gene set were associated with focal adhesion, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and VEGF signaling pathway. Our study created lasting value beyond molecular subtypes and underscored the significance of normal tissues in gastric cancer development, which drawn a novel prognostic model for gastric treatment.

Backgrounds: Noninvasive detection of histological abnormalities remains challenging in patients with HBeAg-negative chronic HBV infection with normal or mildly elevated levels of alanine aminotransferase (ALT). This study aimed to assess the utility of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying significant histological lesions in this population.

Methods: This is a single-center study with retrospective analysis of 392 treatment-naive patients of HBeAg-negative chronic HBV infection with normal or mildly elevated levels of ALT.

Results: In this cohort, significant necroinflammation and fibrosis were found in 69.4% and 61.5% of patients, respectively. Patients with qHBsAg >1000 IU/mL (N = 236) had more hepatic inflammation of ≥G2 (75.4% vs. 60.9%, P < 0.01) or fibrosis ≥ S2 (66.1% vs. 54.5%, P < 0.05) compared to those without (N = 156). Serum HBsAg (cutoff point = 1000 IU/mL), aspartate aminotransferase (AST) level (cutoff point = 25 IU/L), age (cutoff point = 40 years), and HBV family history were identified as independent predictors of significant histological abnormalities in multivariate logistic analysis.

Conclusions: A significantly higher proportion of patients with histological abnormalities were found in patients with qHBsAg >1000 IU/mL than those without. The qHBsAg level together with age, AST, and family history of HBV infection could be used as an algorithm to help noninvasive patient selection for antiviral therapy.

Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients.

Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis.

Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3.

Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.