Introduction

Pancreatic steatosis (PS) has been increasingly recognized and associated with some relevant metabolic implications. However, data on its correlation with exocrine pancreatic function remain limited. We conducted a systematic review and meta-analysis to evaluate whether PS is associated with exocrine pancreatic insufficiency (EPI).

Aims & Methods

This study aimed to investigate whether imaging-detected PS is related to exocrine pancreatic dysfunction, assessed by fecal elastase-1 (FE-1) levels. We searched PubMed, EMBASE, and Cochrane Central for studies including adults with and without PS identified on imaging, and reporting FE-1 concentrations. Data were pooled using random-effects models.

Results

Three studies evaluating a total of 1,864 patients were included. Fecal elastase levels were significantly lower in patients with PS compared to controls, indicating worse exocrine pancreatic function in this group (MD -199.78; 95% CI -303.66 to -95.91; p < 0.05; I² = 97%). Moreover, PS was associated with a significantly increased risk of exocrine pancreatic insufficiency (RR 3.13; 95% CI 1.17–8.40; p = 0.023; I² = 81%), reinforcing the link between fat accumulation in the pancreas and impaired exocrine function.

Conclusion

This meta-analysis demonstrates a significant association between PS and impaired pancreatic exocrine function, compared to individuals without known pancreas disease. These findings underscore the importance of a comprehensive metabolic assessment in patients with PS, given its potential role in pancreatic dysfunction.

Introduction

Recurrent abdominal pain is the predominant symptom of chronic pancreatitis (CP), contributing to significant morbidity and reduced quality of life. Medical management includes analgesics, antioxidants, neuromodulators, and pancreatic enzyme replacement therapy (PERT). While PERT is used for pancreatic exocrine insufficiency (PEI), it is also thought to reduce pain by suppressing pancreatic secretion via negative feedback. However, previous meta-analysis did not show pain reduction, though subgroup analysis suggested potential pain relief with non-enteric (NE) coated enzymes1. Unlike currently available enteric-coated formulations, high in lipase but low in proteas, non-enteric coated enzymes with high protease content dissolve rapidly and may more effectively suppress cholecystokinin-mediated pancreatic stimulation, potentially improving pain outcomes.

Aims & Methods

To primarily assess the effect of a high-protease, non-enteric-coated pancreatic enzyme preparation on pain in patients with painful chronic pancreatitis. The study was registered under ClinicalTrials.gov (NCT05042284).
We conducted a randomized, double-blind, placebo-controlled trial where we randomly assigned participants to a high protease (30,000 U)-containing, non-enteric-coated enzyme preparation (n=54) and a placebo (n=53) group. The study duration was 24 weeks. Patients with painful CP (per Mayo Clinic criteria) with chronic pain were enrolled. The primary outcome was to see a difference in mean Izbicki pain score at 12 and 24 weeks and a change in pain scores (VAS 0-10) using pain diaries. Secondary outcomes were changes in the number of painful days, analgesic requirements, patient’s global impression of change (PGIC), quality of life, and adverse effects. Weekly pain data were collated. Repeated measures, linear, and mixed-effects models were used to analyze the primary outcome. Analysis was intention-to-treat.

Results

107 out of 256 screened patients fulfilled enrollment criteria. The mean age was comparable between groups (35.1±10.6 vs. 33.6±12.3 years; p=0.51), and baseline characteristics were similar. The primary outcome using mixed model analysis showed no significant differences in the change in Izbicki pain scores between the two groups at 12 and 24 weeks (Table: Results). The mean difference in VAS pain score was -3.7(95%CI: -4.3to-3.1) in enzyme group vs. -3.5(95%CI: -4.2to-2.9) in placebo group (p=0.64) at 12 weeks. The changes were -4.2(95%CI: -4.7to-3.6) vs. -4.1(95%CI: -4.7to-3.5), respectively (p=0.79), at 24 weeks indicating no significant difference. The median number of painful days was also similar, at 12 weeks, 16 (IQR: 9–35) in the enzyme group vs. 16 (IQR: 4–36.5) in placebo (p=0.31); at 24 weeks, 3(IQR: 0–8.5) vs. 3(IQR: 0–7)(p=0.30) respectively. Analgesic use was higher in the enzyme group at 12 weeks (45(83.3%) vs. 37(69.8%); p=0.11) and 24 weeks (42(77.8%) vs. 35(66%); p=0.20). Differences in the change in global health status, quality of life, PGIC, and adverse effects at both time points were also non-significant.

Conclusion

Despite the high protease content, Non-enteric coated enzyme preparations did not improve pain and quality of life in patients with painful chronic pancreatitis. Further RCTs are needed to evaluate benefits in distinct subgroups.

References

1. Yaghoobi, Mohammad, Julia McNabb-Baltar, Raheleh Bijarchi, and Peter B. Cotton. “Pancreatic Enzyme Supplements Are Not Effective for Relieving Abdominal Pain in Patients with Chronic Pancreatitis: Meta-Analysis and Systematic Review of Randomized Controlled Trials.” Canadian Journal of Gastroenterology and Hepatology. Doi: https://doi.org/10.1155/2016/8541839

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce weight loss, and have been associated with an overall decreased risk of esophageal cancer. Obesity is strongly associated with esophageal adenocarcinoma and substantial weight loss may decrease the risk of this malignancy, whereas weight loss does not decrease the risk of esophageal squamous cell carcinoma. We examined the hypotheses that GLP-1RA treatment decreases the risk of esophageal adenocarcinoma.

Aims & Methods

This population-based case-control study included all cases of esophageal adenocarcinoma and esophageal squamous cell carcinoma in adults who had dispensed medication for type 2 diabetes in Denmark (2007-2020), Finland (2011-2018), Iceland (2009-2019), Norway (2007-2019), or Sweden (2007-2020). For each case participant, >10 control participants who had dispensed medication for type 2 diabetes were randomly sampled from the general populations. Data came from well-validated nationwide health-data registries with prospectively collected data. Multivariable logistic regression provided odds ratios (OR) for esophageal adenocarcinoma and esophageal squamous cell carcinoma with 95% confidence intervals (CI), adjusted for sex, age, calendar year, country, comorbidity, obesity, alcohol overconsumption, and tobacco smoking.

Results

This study included 2,909 case participants with esophageal adenocarcinoma, 670 case participants with esophageal squamous cell carcinoma, and 55,408 control participants. The risk of esophageal adenocarcinoma was not decreased in GLP-1RA users compared with non-users (adjusted OR 1.3, 95% CI 1.1-1.5). However, the risk of esophageal squamous cell carcinoma was decreased (adjusted OR 0.5, 95% CI 0.3-0.8).

Conclusion

Standard GLP-1RA treatment in patients with type 2 diabetes might not decrease the risk of esophageal adenocarcinoma. Confounding by indication may have been the most important, or even the sole, contributor to the decreased risk of esophageal squamous cell carcinoma observed, although anticarcinogenic mechanisms of GLP-1RAs other than weight loss cannot be ruled out.

Introduction

Both the effectiveness and tolerability of Helicobacter pylori (H.p.) eradication therapy regimens are important in the management of H.p. infection, since the presence of side effects significantly reduces compliance between the doctor and the patient and sometimes can lead to treatment interruption. Our study aimed to compare the efficacy and tolerability of eradication therapy depending on the addition of Saccharomyces boulardii or a synbiotic complex.

Aims & Methods

The study included 78 patients (54 women and 24 men) with confirmed H.p. infection using validated tests, without previous eradication in the anamnesis. All patients underwent a course of eradication therapy, which included proton pump inhibitor (PPI) + amoxicillin (A) + clarithromycin (C) + bismuth subcitrate (B). Patients were divided into 2 groups: in group A (37 patients, 25 women, 12 men, mean age 44±3.2 years) S. boulardii CNCM I-745 was added to the mentioned regimen. In group B (41 patients, 29 women, 12 men, mean age 47±2.8 years), a synbiotic complex containing strains of probiotic bacteria Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus fermentum, Lactobacillus rhamnosus, Lactobacillus casei subsp. сasei, Streptococcus thermophilus, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium adolescentis, Propionibacterium freudenreichii subsp. Shermanii, prebiotics inulin and lactulose were added to the indicated regimen. The duration of eradication therapy was 10 days. The duration of taking the probiotic and synbiotic complex ‒ 15 days.

Results

In group A, the effectiveness of the PPI+A+C+B regimen with the addition of S. boulardii was 75.7%. In group B (with the addition of a synbiotic) - 87.8%. We compared the tolerability of the indicated regimens. In no case (in both groups) was the treatment interrupted due to the presence of serious side effects. In total, 20 (54.1%) patients from group A and 17 patients (41.5%) from group B reported non-serious adverse events, including nausea (group A ‒ 8 patients (21.6%), group B ‒ 6 (14.6%), bitter taste in the mouth (group A ‒ 16 patients (43.2%), group B ‒ 15 (36.6%), and diarrhoea (group A ‒ 6 patients (16.2%), group B ‒ 0 (0%). No other adverse events were documented. Comparing gastrointestinal symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) showed that in group A, mean values of the total score before treatment were 35.9±3.14 points, vs 26.2±1.64 points 20 days after the eradication course (p<0.05). In group B 34.1±2.44 points before treatment, vs 21.7±1.98 points 20 days after the eradication course (p<0.05). Comparing the total score of the GSRS questionnaire after treatment between groups A and B also showed a significant difference: 26.2±1.64 points in group A vs 21.7±1.98 points in group B (p<0.05).

Conclusion

Our study revealed better efficacy (87.8%) of the eradication regimen PPI+A+C+B with the addition of a synbiotic compared to the similar regimen with the addition of Saccharomyces boulardii (75.7%) in patients from Vinnytsia region, Ukraine. In addition, it was found that when the synbiotic complex was added, side effects of eradication therapy were noted in a smaller percentage of patients and significantly (p<0.05) lower values of the total score of the GSRS questionnaire were noted 20 days after treatment, in contrast to the regimen with the addition of Saccharomyces boulardii.