Introduction

The mechanism of aspirin-induced gastric mucosal injury is thought to be mediated by multiple processes involving either topical or systemic effects. Recently, it has been reported that topical effects play a pivotal role in causing gastric mucosal injury. ^{(1, 2)}. It is known that almost all aspirin-induced gastric mucosal injuries were observed in low intragastic pH condition (pH<4) ⁽³⁾. Though it depends on the severity and distribution of gastritis caused by Helicobacter pylori (H. pylori), gastric acid secretion is recovered after the eradication of H. pylori ⁽⁴⁾. Therefore, because intragastric pH may decrease dramatically, the prevalence and severity of gastric mucosal injuries in patients taking aspirin may also change after the eradication.

Aims & Methods

The aim of this study is to reveal the relationship between H. pylori infection and gastric mucosal injuries in patients taking aspirin. This study was a retrospective cross-sectional study. Data were extracted from the records of subjects who underwent upper gastrointestinal endoscopy at our department between April 2015 and March 2020. We focused on the subjects taking only aspirin as an anti-thrombotic agent, and selected the subjects whose H. pylori infection status was known. After that we divided into three groups (non-infection, current infection, and past infection of H. pylori) and compared the severity of gastric mucosal injury, individually. Severity of gastric mucosal injury was evaluated endoscopically based on the modified LANZA score (m-LANZA score). Statistical analyses were performed by using Fisher’s exact test. We evaluated separately for subjects with concomitant use of potassium-competitive acid blocker (P-CAB) or PPI (user) and subjects without concomitant use of P-CAB, PPI nor histamine H2 receptor antagonist (H2RA) (nonuser).

Results

311 subjects out of 6,031 were taking only aspirin as an anti-thrombotic agent. In group of non-infection (43 men, 32 women; mean age 69.0±15.6 years), average MLS was 0.51±1.16 (user: n=45, score0=33, score1=8, score2=1, score3=1, score4=0, score5=2) and 1.21±1.70 (nonuser: n=29, score0=18, score1=0, score2=3, score3=5, score4=1, score5=2). In group of current infection (12 men, 5 women; mean age 67.7±11.4 years), average MLS was 0.86±1.86 (user: n=7, score0=5, score1=1, score2=0, score3=0, score4=0, score5=1) and 1.29±1.89 (nonuser: n=7, score0=4, score1=0, score2=2, score3=0, score4=0, score5=1). In group of past infection (107 men, 51 women; mean age 74.7±7.5 years), average MLS was 0.39±1.07 (user: n=104, score0=86, score1=8, score2=4, score3=2, score4=1, score5=3) and 0.90±1.62 (nonuser: n=49, score0=34, score1=4, score2=3, score3=4, score4=2, score5=4). There was a statistically significantly difference between user and nonuser in group of non-infection (p=0.040) and in group of past infection (p=0.023). Mean MLS in group of current infection was high more than expected because intragastric pH might be high in H. pylori-positive patients. We considered because many subjects which were H. pylori-positive but whose gastric acid secretion was not so impaired might be included in this study.

Conclusion

There was no significant difference between H. pylori infection and gastric mucosal injuries in patients taking low dose aspirin. However, concomitant use of P-CAB or PPI can prevent gastric mucosal injuries in pylori-negative patients taking low dose aspirin.

References

(1) Musumba C, et al. Review article: cellular molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther. 30:517-531 2009
(2) Mashita Y, et al. Oral but parenteral aspirin upregulates COX-2 expression in rat stomachs. a relationship between COX-2 expression and PG deficiency. Digestion. 73:124-132 2006
(3) Nishino M, et al. Relationship between low-dose aspirin-induced gastric mucosal injury and intragastric pH in healthy volunteers. Dig Dis Sci. 55:1627-1636, 2010
(4) El-Omar EM, et al. Helicobacter pylori infection and chronic gastric hyposecretion. Gastroenterology. 113:15-24 1997

Introduction

Gastric dysplasia in the absence of an endoscopically defined lesion is rare, usually either a false positive diagnosis or a previously unidentified precancerous lesion during esophagogastroduodenoscopy (EGD).

Aims & Methods

The aim of this study was to evaluate factors associated with the presence of an endoscopically visible lesion during follow-up in patients with histologic diagnosis of gastric dysplasia in random biopsies.
Retrospective cohort study including patients referred to our institution for gastric dysplasia detected in random biopsies during EGD (Index EGD). In our institution, endoscopic evaluation was performed with a high-definition endoscope using narrow band imaging (HD EGD-0). If no lesion was detected, endoscopic surveillance (HD EGD-FU) was conducted, depending on the originally detected dysplasia: within 6 months for high grade dysplasia (HGD), 12 months for low grade dysplasia (LGD) or indefinite for dysplasia (IFD).

Results

Regarding Index EDG, from a total sample of 96 patients, most patients had LGD (87.4%), 10 patients had IFD (10.4%) and 2 HGD (2.1%), while the location of the dysplasia was the corpus in 8 patients (8.3%), the antrum in 65 (67.7%) and both in 23 (24%).
During the HD EGD-0, 5 (5.2%) presented with an endoscopically visible lesion, while 10 lesions (10.4%) were identified during HD EGD-FU; 80% of the identified lesions were in the antrum.
Patients with Helicobacter pylori infection identified at Index EDG were 8 times more likely to have an endoscopically visible lesion on HD EGD-FU (OR 8.000, 95%CI 1.588-40.299, p=0.012). Additionally, patients with a regular alcohol consumption (≥25 grams daily) were 4 times more likely to have an endoscopically visible lesion on HD EGD-FU (OR 4.063, 95%CI 1.048-15.748, p=0.047). In fact, both Helicobacter pylori infection identified at Index EGD, and regular alcohol consumption were independent predictors of the presence of gastric lesion on HD EGD-FU in binary logistic regression (OR 9.284, 95%CI 1.724-49.979, p=0.009 and OR 5.025, 95%CI 1.136-22.222, p=0.033, respectively).
The grade of dysplasia and location of the biopsies with dysplasia were neither associated with the presence of lesions during follow-up, nor family history of gastric cancer.

Conclusion

The presence of an endoscopically visible lesion occurred in 15.6% of patients with the previous histologic diagnosis of gastric dysplasia in random biopsies and most lesions were identified in the HD EGD-FU. Both Helicobacter pylori infection identified at Index EGD, and regular alcohol consumption were significant predictors of the presence of gastric lesion on HD EGD-FU.

Introduction

A previous study, which found that focal parenchymal atrophy of the pancreas is an indirect sign of small pancreatic cancer (PC), documented the changes in the pancreas until cancer onset.［1-3］ However, the pancreas atrophies and changes with age, so issues remain regarding the criteria for determining pancreatic atrophy as a sign of PC. The application of artificial intelligence (AI) technology to quantify changes in the pancreas over time and predict the onset of PC and high-risk groups for PC from objective indicators has the potential to facilitate early detection of PC.

Aims & Methods

Based on the rate of change in the pancreatic volume on computed tomography (CT) using AI technology, the present study predicted PC onset. Forty patients in whom PC was histopathologically diagnosed at Komagome Hospital between 2015 and 2023 and who had a history of three or more follow-up CT examinations over five years before PC onset (the PC group) were analyzed. Forty patients who underwent CT periodically for malignant skin disease but had no pancreatic disease were enrolled into a non-PC group. Patients with pancreatic carcinoma in situ (pancreatic intraepithelial neoplasm), an intraductal papillary mucinous neoplasm or chronic pancreatitis with multiple calcifications were excluded. Changes in the pancreatic volume in the groups over time were then compared using CT images taken one year or earlier before PC onset. The pancreatic volume was calculated using SYNAPSE VINCENT cloud (Fuji Film, Japan), an AI image application program. Age and pancreas volume were combined to create a scatter diagram, and the rate of pancreatic volume change (the temporal pancreatic volume change coefficient) was calculated from the regression line and compared.

Results

The lesion site in PC group included the head (n=17), body (n=7), and tail (n=16). The median maximum tumor diameter was 31 mm (interquartile range: 27-37). A comparison of the two groups found a cStage classification of IB, IIA, IIB, III, and IV in eight, ten, three, eight, and 11 patients, respectively. The median age was 72.5 and 72.5 years in the respective group (P=0.182). The male: female ratio was 23:17 and 24:16 (P=0.820), the median observation period was 83.5 and 107 months (P<0.05); the mean number of examinations was 10.7 and 18; the total number of CT examinations was 430 and 745; the mean total pancreatic volume was 74.4 and 78.15 ml (P<0.01 ); and the mean pancreatic volume change coefficient was -0.141 and -0.036 (P=0.01), respectively. The rate of decrease in the pancreatic volume was faster in the PC group with increasing age, the average being 8.46 ml over five years in the PC group compared to 2.16 ml in the non-PC group. The cutoff value for the coefficient of pancreatic volume change over time was set at -0.125. The sensitivity was 50%, the specificity was 90%, the positive predictive value was 83%, and the AUC value was 0.67.

Conclusion

In comparison with the age-related changes in the pancreas, the rate of decrease in the pancreatic volume was faster in the PC group, suggesting that PC onset may be predicted using images obtained one year or earlier before PC onset. These findings further suggested that identifying patients with a high risk of PC may be possible by creating a pancreatic volume histogram using AI technology based on age at the time of CT, intervals between past examinations, and the rate of decrease in the pancreatic volume.

References

［１］Nakahodo J, Kikuyama M, Nojiri S, et al. Pancreatology. 2020 Dec;20(8):1689-1697.
［２］Nakahodo J, Kikuyama M, Fukumura Y, et al. Pancreatology. 2022 Dec;22(8):1148-1158
［３］Kikuyama M, Nakahodo J, Honda G, et al. Pancreatology. 2023 Jun;23(4):420-428.

Clinical Case Summary

We describe a case of an 80-year-old woman with a history of bronchiectasis, nasal polyps, and chronic sinusitis who presented to the emergency department with diarrhea(>10 bowel movements/day),abdominal pain and estimated weight loss of 6 kg over one month. She was previously treated with antiparasitics without clinical improvement. Laboratory tests showed peripheral eosinophilia(10,400/mm3 eosinophils, 51.4% of total leukocytes). Viral serologies and autoimmune study were negative. Microbiological and parasitological analyses of stool samples were negative too. Immunoglobulin E levels were elevated. Abdominal computed tomography(CT) revealed thickening of the rectal ampulla and sigmoid colon. Upper gastrointestinal endoscopy did not show any abnormalities, but rectosigmoidoscopy revealed colorectal mucosa with millimetric whitish dots, some scattered erosions, and a 20 mm ulcer in the distal rectum that was biopsied. Histological evaluation showed inflammatory changes with predominance of eosinophilic polymorphonuclear cells(>50/field). Bone marrow study showed eosinophilic myeloid hyperplasia without blasts. No cytogenetic abnormalities were identified on chromosomal analysis. During hospitalization, she developed pruritic erythematous macules on the sacral region and inner thighs that gradually improved with topical steroids. Idiopathic hypereosinophilic syndrome with gastrointestinal involvement and possible cutaneous and pulmonar, was assumed. Prednisolone 40 mg/day was started with clinical and laboratory improvement, with complete resolution of peripheral eosinophilia. The diagnosis of idiopathic hypereosinophilic syndrome is a challenge because it is a diagnosis of exclusion and manifests in various ways depending on the affected system, with gastrointestinal involvement being possible, as in the case presented here. Recognition and early initiation of appropriate treatment can improve the survival and quality of life of these patients.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. Major adverse cardiovascular events (MACE) have been associated with diseases of chronic inflammation. Data on MACE from large population-based cohorts of biopsy-proven EoE are lacking.

Aims & Methods

The aim of this study was to investigate the association between EoE and MACE. It included all Swedish adults with EoE (1990-2017) without a record of previous cardiovascular disease (CVD) (n=1,546, with follow-up until 2019). EoE was defined from prospectively recorded esophageal histopathology reports from all Swedish pathology departments (n=28) in the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Individuals with EoE were matched with up to five general population reference individuals (n=7,281) for age, sex, calendar year and county without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACEs (any of ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. In secondary analyses, individuals with EoE were compared to their siblings to account for residual confounding.

Results

The majority of individuals with EoE were male (75%), and the median age at EoE diagnosis was 37 years (IQR 19-51). Over a median of 6.0 (IQR 4.6-8.0) years of follow-up, 65 (4.2%) MACE events were observed in patients with EoE and 225 (3.1%) in reference individuals, corresponding to 6.4 vs. 4.7 events per 1,000 person-years (incidence rate difference: 1.7, 95%CI=0.0-3.4), respectively. No significantly higher overall risk (aHR=1.14, 95%CI=0.86-1.51) of MACE outcomes. No significant differences between age, sex and follow-up time were observed. When adjusting for relevant CVD medication and sibling comparison, results were similar.

Table 1 Incidence Rates, Absolute Rate Differences and Hazard Ratios for incident Major Adverse Cardiovascular Events in patients with Eosinophilic Esophagitis compared to general population reference individuals 1990-2019
		Reference individuals	EoE
		N=7 281	N=1 546
	MACE outcomes*
	Incident events (%)	226	65
	Incidence rate per 1000 py (95%CI)	4.7 (4.1-5.4)	6.4 (4.9-8.1)
	Absolute rate difference per 1000 py (95%CI)	0 (ref.)	1.7 (0-3.4)
	Unadjusted HR# (95%CI)	1 (ref.)	1.37 (1.04-1.80)
	Adjusted HR (95%CI)	1 (ref.)	1.14 (0.86-1.51)

CI, confidence interval; EoE, eosinophilic esophagitis; HR, hazard ratio; MACE, major adverse cardiovascular events; py, person-years

^*Includes ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality.
^#Adjusted for age, sex, calendar year, county of residence at index date, country of birth (Nordic country or other), educational level (compulsory school, upper secondary school or college/university), ≥1 metabolic disease (diabetes, obesity, hypertension or dyslipidemia), chronic kidney disease, atopic dermatitis, celiac disease and chronic respiratory disease (chronic obstructive pulmonary disease or asthma) diagnosis.

Conclusion

Individuals with biopsy-proven EoE had no increased risk of MACE outcomes compared to general population or sibling comparators. The absence of any association with MACEs in our study may be reassuring for patients with EoE.

Disclosure

Dr. Forss has served as a speaker and advisory board member for Janssen corporation. Dr. Uchida is a medical advisor for Sanofi-Regeneron and AstraZeneca. Dr. Roelstraete has no conflicts of interest. Dr. Ebrahimi has served as advisory board member for Boehringer Ingelheim. Dr. Garber do not have any conflicts of interest to declare related to this study. Dr. Sundström reports stock ownership in Anagram kommunikation AB and Symptoms Europe AB outside the submitted work. JFL has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). This study received funding from Janssen corporation. JFL has also received financial support from MSD to develop a paper reviewing national healthcare registers in China, and has ongoing discussions with Takeda about a celiac disease project.