Introduction

Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are widely used to evaluate gallbladder disease.
However, there are some cases difficult to diagnose even with those modalities. In recent years, the image quality of diffusion-weighted imaging (DWI) has improved with the development of MRI systems. The usefulness of DWI for gallbladder disease has been reported in several studies. PET has some limitations, such as high cost, radiation exposure, and influence by blood glucose levels. The purpose of this study was to compare the usefulness of DWI with PET in the diagnosis of gallbladder disease.

Aims & Methods

Forty-two patients who underwent preoperative DWI and PET for gallbladder disease were included. The final diagnosis was made histologically on excised specimens. Of the 42 patients, 24 had malignant conditions (23 had gallbladder cancer, and 1 had neuroendocrine cancer), and 18 had benign conditions (9 had chronic cholecystitis, 3 had adenomyomatosis, 4 had polyps, 1 had gallbladder adenoma, and 1 had xanthogranulomatous cholecystitis). We evaluated the accuracy of DWI and the apparent diffusion coefficient (ADC) value of each disease.

Results

The sensitivity of DWI and PET was 88% vs 88% (p = 1.0), the specificity was 61% vs 56% (p = 0.56), and the accuracy was 76% vs 74% (p = 0.56), showing no significant difference. The mean ADC value of malignant diseases was (1.71±0.29) × 10-3mm2/s, and that of benign diseases was (2.33±0.36) × 10-3mm2/s (p < 0.001). The mean ADC value of malignant diseases was significantly lower than that of benign diseases.

Conclusion

In this study, DWI had a similar accuracy compared to PET. DWI compensates for the limitations of PET and can be performed in a more noninvasive manner. The combined use of DWI and ADC was suggested to contribute to the improvement of the diagnostic capability for gallbladder diseases.

References

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Introduction

Critically ill patients are at high risk for upper gastrointestinal (GI) bleeding.¹ Proton pump inhibitors (PPIs) are commonly used for prophylaxis, but their safety and efficacy compared to histamine-2 receptor antagonists (H2 blockers) and placebo remain unclear.^1–4

Aims & Methods

Our systematic review and meta-analysis aims to assess the safety and efficacy of PPIs for preventing upper GI bleeding in critically ill adults. We conducted a comprehensive search of Scopus, Web of Science, PubMed, and Cochrane Central for relevant randomized controlled trials (RCTs) from inception until March 2024. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and Odds ratio (OR) for dichotomous data in a random-effect model meta-analysis, using R software.

Results

Nineteen RCTs were included in this meta-analysis with a total of 62221 patients. Our study showed that PPI was superior to control in terms of GI bleeding [RR 0.55, (95% CI, 0.42 to 0.72); P = <0.01]. However, the overall effect did not favor either of the two groups in terms of ICU, mortality rate, and nosocomial infection [MD -1.45, (95% CI, -5.31 to 2.42); P = 0.4], [RR 1.04, (95% CI, 1.00 to 1.09); P = 0.07], and [RR 1.27, (95% CI, 0.98 to 1.65); P = 0.07], respectively.

Conclusion

In conclusion, our findings demonstrated a significant reduction in GI bleeding risk associated with PPI use. At the same time, we did not find a statistically significant difference between PPI and control groups regarding ICU mortality rate, overall mortality rate, or nosocomial infection rates. These findings suggest that PPIs may be effective in reducing upper GI bleeding in critically ill patients. However, further research might be necessary to definitively determine the impact of PPIs on mortality and infection risks in this population.

References

.1. Wang Y, Ye Z, Ge L, et al. Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: Systematic review and network meta-analysis. The BMJ. 2020;368. doi:10.1136/bmj.l6744
2. Kondo Y, Ohbe H, Matsui H, Fushimi K, Tanaka H, Yasunaga H. Proton pump inhibitors versus histamine-2 receptor antagonists for stress ulcer prophylaxis during extracorporeal membrane oxygenation: a propensity score-matched analysis. BMJ Open. 2020;10(9):e037534. doi:10.1136/bmjopen-2020-037534
3. Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: A systematic review and meta-analysis of randomized trials. Crit Care. 2016;20(1). doi:10.1186/S13054-016-1305-6
4. Jung YS, Park JH, Park CH. Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta-analysis. United European Gastroenterol J. 2023;11(9):861-873. doi:10.1002/ueg2.12448

Introduction

Fecal calprotectin (FC) is a key non-invasive biomarker used to monitor inflammatory bowel disease (IBD). Despite its clear clinical value, patient adherence to the test remains suboptimal, mainly due to reluctance related to stool collection. The objective of the ACCALMI study was to compare the acceptability of a new stool collection device, similar to the one used for fecal immunochemical tests (FIT), with a standard stool container, and to evaluate its impact on patient compliance.

Aims & Methods

In this prospective, single-center study, 156 patients with an established diagnosis of IBD and who had been prescribed an FC test as part of their routine care, were randomly assigned to either the standard container group or the alternative device group (Procise Stool Collection Device™), which includes a collection tube with a thin spiral-shaped probe facilitating stool collection. Acceptability was assessed using a 4-category ordinal scale (from "poor" to "very good") and a visual analog scale (VAS, from 0 to 10). Analyses were conducted in both per-protocol and intention-to-treat (ITT) populations, with missing data handled using the maximum bias method. Factors associated with improved FC acceptability, and compliance with FC testing, were analyzed.

Results

The alternative collection device significantly improved acceptability as measured by the ordinal scale (odds ratio [OR] 2.69; p < 0.001). In the alternative group, acceptability ratings were significantly higher with only 1.4% versus 7.0% rating it as ‘poor’, 12.5% versus 46.6% as ‘average’, 66.7% versus 40.8% as ‘good’, and 19.4% versus 5.6% as ‘very good’. Measured using the VAS, the average acceptability was 7.9/10 in the group using the alternative device compared to 6.1/10 in the standard group, with a significant difference of 30.4% (95% CI [19.7 - 44.7%], p < 0.001), although it did not reach the threshold of 30% that was set a priori. The ITT analysis led to the same conclusions. Among the patients who had already undergone FC testing and were randomized to the "alternative device" group, 55% indicated a preference for the alternative device, compared to 7.2% for the conventional device, while 37.7% found them similar. Embarrassment and discomfort associated with the standard container were alleviated by the alternative device. A long home-to-hospital distance (> 50 km) and the use of the alternative device were the only factors associated with better acceptability in the multivariate analysis. Compliance was similar between both groups and remarkably high (92%).

Conclusion

The ACCALMI study demonstrated that the alternative stool collection device, similar to the one used in FIT for colorectal cancer screening, is more accepted by IBD patients than the standard container, thus improving the acceptability of FC testing. These findings support the integration of patient-centered innovations in diagnostic and follow-up testing to improve the monitoring of IBD.

Disclosure

Acknowledgments: Collaboration with Biosynex®.

Introduction

Proton-pump inhibitors (PPIs) are the most prescribed first-line treatment for eosinophilic esophagitis (EoE). However, only around half of patients respond histologically to a double dosage of PPI (1). Pharmacogenetics of PPIs is largely known to depend on CYP2C19 haplotypes (2). Previous studies in EoE have shown promising results to predict PPI response by analyzing genetic variations in CYP2C19 and STAT6 genes, while other single nucleotide variations (SNPs) could play also a role (3).

Aims & Methods

The study aims to analyze the effect of 60 previously described SNPs associated with the response to PPIs in EoE or other diseases, or related to EoE genetics. Those SNPs were genotyped using an Open Array platform on DNA obtained from peripheral blood. Inclusion criteria were patients diagnosed with EoE according to clinical guidelines and treated with PPIs. Exclusion criteria were: response not evaluated under double or higher PPI doses, lack of histopathologic response assessment or unresponsiveness to PPIs before 8 weeks of treatment length. Patients were recruited in 4 Spanish referral hospitals and demographical and clinical data were obtained retrospectively. Patients were classified as non-responders (peak of eosinophils ≥15 per high power field, hpf) or responders (<15 eos/hpf). Chi-square or Fisher’s exact test were used for statistical comparisons. Statistical significance was established for p<0.05.

Results

Overall, 505 patients (75% male and 15% <18 years-old at PPI onset, mean age 34.5 ± 14.9 years) were included; 48% responded to double o higher PPI doses. Omeprazole was the most common PPI (57%). Seventeen percent of patients presented mixed or stricturing EoE phenotypes.
Regarding clinical variables, sex and age did not influence PPI effectiveness. In concordance with previous studies, a lower response rate was found in patients with mixed/structuring compared with inflammatory phenotypes (27% vs 52%, p<0.001). Treatments length over 10 weeks achieved higher effectiveness (p=0.028). Using omeprazole and rabeprazole trended to produce higher effectiveness (p=0.067).
Two SNPs were found to be associated with response to double or higher PPI doses: CYP3A5 rs776746 (p=0.013, intermediate phenotype associating to a lower response rate of 35%, and being present in 14% of patients) and KCNJ2 rs312691 (recessive model, p=0.006, this variant increasing response up to 69%, and being present in 8% of patients).
Since phenotype had a great influence in response to PPIs, patients’ genotypes were analyzed according to this variable. The 2 aforementioned variants had no effect on mixed/stricturing phenotypes, while statistical significance was kept for CYP3A5 rs776746 and KCNJ2 rs312691 in patients with inflammatory phenotypes (p=0.007 and p=0.005, respectively). For patients with mixed/stricturing phenotypes, the presence of variants in chr14 rs7144958 (dominant model), STAT6 rs3024974 (recessive model) or being a CYP2C19 rapid/ultrarapid metabolizer (frequency of 18%, 19% and 28% in this type of patients, respectively) produced a trend to unresponsiveness to PPI (93%, p=0.097; 92% p=0.100; and 86%, p=0.094, respectively).
On the other hand, when sub-groups were created according to PPI drug, the use of esomeprazole in patients carrying the CYP3A5 rs776746 variant further reduced the response rate to only 19% (p=0.072).

Conclusion

We have identified two SNPs affecting the response to double or higher doses of PPI in EoE patients with inflammatory phenotype and three SNPs that may decrease PPI effectiveness in patients with mixed or stricturing phenotypes.

References

1. Laserna-Mendieta EJ, Casabona S, Guagnozzi D, et al. Efficacy of Proton Pump Inhibitor Therapy for Eosinophilic Oesophagitis in 630 Patients: Results from the EoE Connect Registry. Aliment Pharmacol Ther 2020, 52:798–807.
2. Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther 2021, 109:1417–1423.
3. Rodriguez-Alcolado L, Navarro P, Arias-Gonzalez L, et al. Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics. Pharmaceutics 2024, 16:487.

Clinical Case Summary

Introduction: Gastric siderosis (GS) refers to the abnormal deposition of iron within the gastric mucosa, a condition that can be associated with various underlying pathologies. Our case depicts a case of gastric siderosis with iron deposition in the stomach in association with excessive oral iron intake, presenting unusually with chronic diarrhea. Such association has been mentioned previously in the literature but not established.
Case: A 70-year-old lady with a history of iron deficiency anemia and chronic kidney disease presented with 3 weeks of progressively worsening diarrhea. Home medicines included iron pills. She denied any blood in stool, abdominal pain, recent travel, or antibiotic use. Her vitals and her abdominal exam were unremarkable. Stool studies, including stool parasite, C. difficile toxin, calprotectin, and bacterial PCR, were negative.
Colonoscopy showed a normal macroscopic appearance with random biopsies negative for microscopic colitis. An upper endoscopy was performed demonstrating normal esophagus but pitted brown spots mucosa in the gastric body, and antrum. Biopsies were taken, with antral ones demonstrating antral mucosa with iron deposition in the glands and lamina propria concerning gastric siderosis. Oral iron was discontinued and the patient endorsed improvement in symptoms upon outpatient follow-up with endoscopic resolution at 6 months.
Discussion: Iron deposition in gastric mucosa induces a highly oxidative state, producing injury. However, siderosis due to oral iron use is less commonly associated with mucosal injury, with cases seen with changes ranging from erythema to mucosal erosions. Our patient had pattern B on biopsy involving stroma, whereas A involves macrophages in gastric inflammation, and C involves glands in hemochromatosis. No association with the duration or amount of exposure is associated with differences in symptoms. Non-bloody diarrhea occurs without active ulceration being reported, making our patient unique.

References

1. Marginean EC, Bennick M, et al. Gastric siderosis: patterns and significance. Am J Surg Pathol. 2006 Apr;30(4):514-20. doi: 10.1097/00000478-200604000-00013. PMID: 16625099.
2. Abraham SC, Yardley JH, Wu TT. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol. 1999 Oct;23(10):1241-7. doi: 10.1097/00000478-199910000-00009. PMID: 10524525.
3. Siah CW, Ombiga et al. Normal iron metabolism and the pathophysiology of iron overload disorders. Clin Biochem Rev. 2006 Feb;27(1):5-16. PMID: 16886043; PMCID: PMC1390789.
4. Idoate Gastearena MA, et al. A comparative study on the gastroduodenal tolerance of different antianaemic preparations. Hum Exp Toxicol. 2003 Mar;22(3):137-41. doi: 10.1191/0960327103ht330oa. PMID: 12723894.
5. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011 Mar 15;434(3):365-81. doi: 10.1042/BJ20101825. PMID: 21348856; PMCID: PMC3048577.
6. Hattori H. High prevalence of haemosiderin accumulation in the cytoplasm of gastric glands in patients with liver cirrhosis. J Clin Pathol. 2004 Jun;57(6):621-4. doi: 10.1136/jcp.2003.010405. PMID: 15166268; PMCID: PMC1770335.
7. De Petris G, Gatius Caldero S, et al. Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II). Int J Surg Pathol. 2014 Apr;22(2):120-8. doi: 10.1177/1066896913502229. Epub 2013 Sep 10. PMID: 24021899.

Clinical Case Summary

We present the case of a 50-year-old man with six months of persistent, non-bloody watery diarrhea (8–10 episodes/day), unresponsive to antibiotics and probiotics. His past medical history was unremarkable, he took no home medications, and denied raw meat or fish consumption. Notably, he had recently started working in an animal feed production facility one month before symptom onset. Initial labs showed mild leukocytosis (10.04 x 10³/µL; ULN: 8.77) and mildly elevated CRP (7.5 mg/L; ULN: 3.4). Extensive infectious workup, including CMV serology, Quantiferon, stool cultures for Salmonella, and tests for fungi and parasites (e.g., Giardia), fecal elastase, rectal swabs for Klebsiella pneumoniae carbapenemase and Clostridium difficile returned negative. Colonoscopy and upper GI endoscopy were normal, and biopsies from all intestinal segments showed no pathological findings. He was discharged with partial improvement (3–4 bowel movements/day) and normalized CRP, but was readmitted a week later for worsening symptoms. Repeat blood work, thyroid function, serum calcitonin and inflammatory markers were within normal limits. Intestinal ultrasound showed a tubular descending colon suggestive of nonspecific left-sided colitis; other bowel segments were normal. Stool tests remained negative.Urine toxicology was positive for cannabinoids. Upon further questioning, the patient admitted to regular use over the past eight months, including during both hospitalisations (CUDIT-R score = 12). After cessation of cannabinoid use, diarrhea resolved completely. At 3-month follow-up, he was asymptomatic, with normal bowel habits and labs. He reported only sporadic cannabinoid use at present (CUDIT-R score 7). This case illustrates the potential for chronic cannabinoid use to induce persistent diarrhea mimicking infectious or inflammatory disease. Screening for substance use should be considered in chronic unexplained diarrhea.