Introduction

The current gold standard for diagnosis of Inflammatory bowel disease (IBD) is based on clinical and endoscopic evaluation as well as histologic and radiologic evaluation. However, endoscopic evaluation can be uncomfortable and carry some risks, especially in the pediatric population that requires general anesthesia in order to perform the procedure.

Aims & Methods

Our aim was to investigate whether serum biomarkers can differentiate between pediatric patients with and without IBD. Secondary aims were to determine whether there are biomarkers that can differentiate between Crohn's disease (CD) and Ulcerative colitis (UC), and whether we can predict progression to biologic treatment within one year from diagnosis using these biomarkers.
Pediatric patients undergoing a first diagnostic colonoscopy at British Columbia Children's Hospital (BCCH) between December 2019 and June 2022 were invited to participate in the study. A 2 ml blood sample was taken from each participant at the time of colonoscopy. Demographic and clinical data were collected from each patient. Blood samples were analyzed using the Legendplex^TM flow cytometry kits investigating which included 50 different inflammatory cytokines and chemokines associated with IBD. A prediction model was built via a supervised learning method to determine how well we can predict the different groups.

Results

One hundred pediatric patients participated in the initial study. Five were excluded from the analysis due to uncertain diagnosis. Median age was 13.36 years, 39 were females (41%) and 54 (56.84%) were diagnosed with IBD, with 35 (64.81%) diagnosed with Crohn's disease. On a univariate analysis and Volcano plot 6 biomarkers were found to be strongly associated with the diagnosis of IBD: IL22, IL8, TARC, GROA, MIG, and IL18. The cross-validated AUROC was 0.70. Using SPLS-DA the classification accuracy was improved to 0.84, and MIG was found to be the key biomarker to discriminate between pediatric IBD patients and non-IBD patients.
On a univariate analysis only TSLP was found statistically significant as a predictor of CD, and RANTES and TARC were found as negative predictors for initiating biologic treatment within one year of diagnosis. However, the prediction model did not predict well the subclasses nor progression to biologic treatment.

Conclusion

Using serum biomarkers can predict the diagnosis of Pediatric IBD. MIG was found to be the key biomarker in the prediction model.

Introduction

Gastric adenoma is recognized as a premalignant lesion.¹Much of the literature lumps all adenomas together with different classifications. These are few western reports regarding the prevalence, associated risk factors and outcomes of endoscopic management of different subtypes of gastric adenoma.

Aims & Methods

Aims: The aim of this study is to determine the prevalence, potential predictors, and outcomes of endoscopic management of the different subtypes of gastric adenoma.
Methods: Of 162 consecutive patients who underwent endoscopic resection for gastric lesions between 2017 and 2022 at our center, 79 patients were enrolled. All the hyperplastic polyps (n=37) and subepithelial lesions (n=46) were excluded. The patient clinical characteristics, endoscopic and histopathological features of gastric lesions were retrospectively collected. Patients were divided according to the histological types of gastric adenoma into 4 groups: intestinal group (n= 49), foveolar group (n= 23),pyloric group (n= 6) and oxyntic group (n=1). We statistically compared the clinical and endoscopic features of the three groups. In addition to the analysis of the outcomes of endoscopic resection of gastric adenomas.

Results

Of the 79 patients with a mean follow-up of 2622 months, 51 patients were males (65 %) and 28 patients were females (35%). Forty-nine patients (49/79,62%) had intestinal adenoma, 23 patients (29%) showed foveolar adenoma, 6 patients (8%) developed pyloric adenoma and only 1 patient (1%) had oxyntic adenoma. The mean age was significantly older in the intestinal group (71 ± 13 years vs. 64 ± 16 years vs. 58 ± 18 years, p = 0.03). Intestinal adenomas were significantly associated with family history of gastric adenocarcinoma (14% vs. 4% vs. 0%, p = 0.01) and history of statin intake (39% vs. 26% vs. 0%, p = 0.04).Foveolar adenomas were significantly associated with multiple lesions (≥3 lesions) (p < 0.001) and 0-IIa+IIc Paris classification (6/23, 26%). the size of largest polyp was significantly higher among pyloric group (28 ±15, p= 0.00). Among intestinal group, 33/49 patients (67%) had atrophic gastritis. 82% of the adenomas were resected by ESD with histologically complete resection (R0) in 72/79 patients (91%). Although the difference was not statistically significant (p = 0.4), adenocarcinoma was most frequently encountered among the intestinal adenoma group (17/49, 35%). The post endoscopic resection outcome was comparable among 3 groups with overall recurrence rate (group1:8% vs. group 2:17% vs group 3:17%, P = 0.07) with a comparable mean time to recurrence among three groups (21 ± 17 months vs. 20±17months vs. 14 months, p=0.8). Family history of gastric adenocarcinoma (HR=1.33, p< 0.001) and active helicobacter pylori infection (HR=1.14, p < 0.001) were identified as independent predictors of recurrence after endoscopic resection of different gastric adenoma. Among baseline endoscopic characteristics, polyp size ³ 30mm(HR= 2.04, p< 0.001), more than 3 polyps (HR=1.51, p<0.001), lesser curvature as lesion location (HR=1.72, p< 0.001) and morphology as Paris classification IIc are potential predictors of post resection recurrence. In addition to specimen size ³ 15mm (HR=2.19, p< 0.001) and T1b as lesion histology (HR=2.07, p< 0.001), in the histopathological examination.

Conclusion

The present study clarifies the endoscopic and histopathological characteristics of different gastric adenomas, in addition to the potential predictive factors for each subtype. Potential predictors of recurrence after endoscopic resection emphazie the importance of endoscopic follow up.

References

1. Fujiwara, Y. et al. Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection. Endoscopy 28, 425–430 (1996).

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectal cancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC. C57/BL6 wild-type (WT), Il33^-/-, T1/St2^-/- and Nt5e^-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well as endoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2 localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33^-/- and T1/St2^-/-. qPCR analysis was done on isolated polyps from WT, Il33^-/- and T1/St2^-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well as IL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33^-/- and T1/St2^-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33^-/- and T1/St2^-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e^-/- showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotes tumorigenesis in colitis-associated CRC through the activation of CD73. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease with unknown causes. Patients experience periods with active disease and symptoms such as diarrhoea, pain and weight loss. Little is known about environmental factors that trigger flare-ups, including the effects of commonly used medications. Recent studies suggest a link between microbial factors and IBD, making it important to investigate the impact of antibiotics on flare-ups.

Aims & Methods

We aimed to investigate whether certain antibiotics increase the risk of flares in patients with IBD. We utilized a previously described¹ cohort of all patients with IBD in Denmark between 1974 and 2018. The cohort is based on the Danish Nationwide Patient Registry, which registers all healthcare related visits, treatments and procedure on an individual level. We utilized data between 1994 and 2018 and two distinct cohorts was created for the purpose of identifying flares. The first cohort was characterized by having an IBD-related hospital stay. The second cohort was characterized by experiencing a flare of IBD in need of systemic steroids. Patient were matched 1:5 using K-nearest neighbour. Antibiotics were grouped into the 3rd level of the Anatomical Therapeutic Chemical (ATC) classification system, with anthelmintics grouped into the 2nd level due to low numbers and all given within 60 days before the outcome. Logistic regression analysis was used to calculate odds ratios (ORs) with a 95% confidence interval (95% CI), with adjusting variables including year of remission/flare, sex, age at diagnosis, year of diagnosis, type of IBD, socioeconomic status², use of 5-ASA, use of budesonide, use of immunosuppressants, and use of subtypes of biologics.

Results

There were in total 69,908 IBD patients in the original cohort. After applying the abovementioned algorithm, a total of 15,636 and 5,178 patients were included in the cohort for hospitalisation and steroid use, respectively.
Using a multivariate logistic regression model, both cohorts observed a significant increase in odds ratios for certain antibiotics in relation to hospitalization and steroid course. Specifically, for the need of a course of steroids, quinolones (OR 3.83 (95% CI: 2.73-5.35)), antimycotics (OR 2.30 (95% CI: 1.53-3.40)), agents against amoebiasis and protozoal (OR 2.06 (95% CI: 1.39-3.01)), betalactam antibiotics (OR 1.35 (95% CI: 1.10-1.66)), and intestinal anti-infectives (OR 2.12 (95% CI: 1.08-3.98)) were associated with an increased risk for a flare requiring steroids.
Regarding the need for an IBD-related hospitalization, agents against amoebiasis and protozoal (OR 3.48 (95% CI: 2.72-4.44)), quinolones (OR 3.10 (95% CI: 2.48-3.86)), intestinal anti-infectives (OR 2.42 (95% CI: 1.54-3.76)) and antimycotics (OR 1.58 (95% CI: 1.17-2.12)) were all found to be significantly associated.

Conclusion

This study provides evidence that certain types of antibiotics increase the risk of flare-ups in patients with IBD. Quinolones, antimycotics, agents against amoebiasis and protozoal, betalactam, and intestinal anti-infectives were all associated with increased odds ratios for hospitalization and a need for a course of steroids. These findings highlight the importance of carefully considering the use of antibiotics in IBD patients and the need for further research on the effects of different antibiotics on disease progression.

References

¹ Lo B, Zhao M, Burisch J. Identifying patients with inflammatory bowel disease in the Danish National Patient Register. Dan Med J. 2023 Mar 27;70(4):A07220458. PMID: 36999818.
² https://www.dst.dk/en/Statistik/dokumentation/nomenklaturer/socio

Disclosure

An unrestricted grant was received from the Aage og Johanne Louis-Hansens Fond to support this study.

Clinical Case Summary

A 39-year-old woman was admitted on June 20, 2024, with a right middle cerebral artery stroke, nine weeks after starting Upadacitinib for ulcerative colitis. She presented with dysarthria, dysphagia, and severe left-sided weakness. CT imaging revealed a wedge-shaped infarction without intracranial hemorrhage (CT head/ Brain MRI).
She was diagnosed with ulcerative colitis in November 2023, she initially responded to Mezavent and steroids but was hospitalized on March 31, 2024 for moderate UC flare, requiring infliximab rescue therapy. The patient presented with four bloody bowel movements and elevated inflammatory markers (CRP>100), confirmed by a Mayo score of 2 on flexible sigmoidoscopy and cytomegalovirus (CMV) infection was excluded. Clostridium difficile tests were negative twice and a CT scan revealed pancolitis. Despite minimal response to rescue therapy, she opted for medical treatment over colectomy.
On April 23, 2024, she began an eight-week induction of Upadacitinib 45 mg, which she tolerated well. However, on June 20, she developed sudden stroke symptoms while eating dinner, including difficulty swallowing, choking, left-sided weakness, and numbness. She had no vascular risk factors or family history of premature cardiovascular conditions. Lupus, and vasculitis work up were unremarkable and extensive thrombophilia screenings were all negative.
Discussion: Thrombosis in IBD patients can result from various potential causes. First of all, Inflammation and hypercoagulability, driven by elevated cytokines like TNF, interleukins, and CRP, activate the coagulation cascade, increasing thrombosis risk.
Conclusion: IBD is a known risk of thromboembolic disease, this risk increased during flare up will raise future research questions regarding extended anticoagulation prophylaxis during flare and uses of Jak stats inhibitor.

References

1. Ferro JM,Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci. 2021 May 15;424:117426. doi: 10.1016/j.jns.2021.117426. Epub 2021 Mar 27.

2. Solitano V.Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets. 2021;22(1):126-136. doi: 10.2174/1389450121666200902164240.

3. Guiu A,a new opportunistic pathogen associated with cystic fibrosis?]Enferm Infecc Microbiol Clin. 2014 Oct;32(8):497-501. Spanish.DOI: 10.1016/j.eimc.2013.08.003

4. Tan JT, Ng DP.Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.Diabetes. 2009 Jun;58(6):1445-9.DOI: 10.2337/db08-1138

5. Reddy VB.The burden of diverticular disease on patients and healthcare systems.Gastroenterol Hepatol (N Y). 2013 Jan;9(1):21-7.

6. Kim WJ.Major constituents and antimicrobial activity of Korean herb Acorus calamus.Nat Prod Res. 2011 Aug;25(13):1278-81.DOI: 10.1080/14786419.2010.513333

7. Lou JS, Effect of expectancy and personality on cortical excitability in Parkinson's disease.Mov Disord. 2013 Aug;28(9):1257-62.DOI: 10.1002/mds.25471PMID: 23630185

8. Parra-Izquierdo I,Janus kinase inhibitors ruxolitinib and baricitinib impair glycoprotein-VI mediated platelet function.Platelets. 2022 Apr 3;33(3):404-415.DOI: 10.1080/09537104.2021.1934665Epub 2021 Jun 7.

9. Kwak SH, Incidentally found resectable lung cancer with the usage of artificial intelligence on chest radiographs.PLoS One. 2023 Mar 10;18(3):e0281690.DOI: 10.1371/journal.pone.0281690PMID: 36897865;

10. Nguyen GC, et al. Consensus Statements on the Risk, Prevention, and Treatment of Venous Thromboembolism in Inflammatory Bowel Disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835–848. doi:10.1053/j.gastro.2014.01.042

Introduction

Acute pancreatitis (AP) is a common cause of acute hospital admissions, with the potential for severe acute complications, progression to chronic pancreatitis and recurrent episodes. A first presentation leads to investigations to identify a cause, including serum blood tests and transabdominal ultrasound. Following these investigations, a significant minority of patients have no clear cause for pancreatitis. Endoscopic ultrasonography (EUS) can identify aetiologies of AP, and direct intervention to reduce recurrence. The goal of this study was to determine the diagnostic yield of EUS and the impact of subsequent biliary intervention on recurrence of AP.

Aims & Methods

This was a retrospective service evaluation of EUS referrals to a regional referral centre in the UK from January 2015 to December 2019. Demographics, symptoms, liver blood tests, non-invasive imaging, EUS records and outcomes were reviewed. A EUS was labelled as diagnostic if findings were identified which explained the cause for pancreatitis that had not been explained with other investigations. Symptom resolution was defined as no further episodes of acute pancreatitis or abdominal pain requiring investigation, imaging, or presentation to secondary care during the follow-up period. Statistical significance for the difference between proportions was calculated using chi-squared tests.­­­­­­­­­­

Results

Ninety-seven patients were included in the study. The median age of the cohort was 58 (range 18-88) years. 55 (57%) patients were male. 22/97 (23%) patients had previously had a cholecystectomy. 41/97 (42%) had abnormal liver blood tests at the time of referral. Three patients had no non-invasive imaging. 27/97 (28%) had one of either transabdominal ultrasound, MRCP or CT, 63/97 (65%) had two tests and 4/97 (4%) had all three. 5 (5%) patients previously had a non-diagnostic EUS.
72/97 (74%) EUS were diagnostic. Findings included gallstones (n=15), gallbladder microlithiasis/sludge (n=51), bile duct stones (n=13), bile duct microlithiasis/sludge (n=11), chronic pancreatitis (n=7) and a pancreatic mass (n=1) which was later diagnosed as a pancreatic adenocarcinoma.
65 patients had a biliary aetiology for their pancreatitis which was amenable to treatment. Of these, 12 had subsequent ERCP, 7 had ERCP and cholecystectomy, 33 had a cholecystectomy and 13 were treated conservatively. Recurrent pancreatitis occurred in 12/52 (23%) patients who had treatment for a biliary aetiology of their pancreatitis compared with 8/13 (75%; p<0.01) of patients who were managed conservatively despite a biliary aetiology for pancreatitis, 8/32 (25%; p=0.84) of patients with a diagnostic EUS with a finding not amenable to treatment or a non-diagnostic EUS experienced further episodes. One patient died from complications related to acute pancreatitis and was not included in this analysis. Median duration of follow-up was 51 months (range 32-80 months).

Conclusion

In our cohort of patients referred for EUS for unexplained acute pancreatitis, EUS had a high diagnostic yield. A lower proportion of patients had a biliary aetiology for their pancreatitis that was amenable to intervention with either ERCP, cholecystectomy or both procedures; these patients experienced fewer episodes of recurrent acute pancreatitis than those managed conservatively. This supports the use of EUS in patients with acute pancreatitis with no cause identified with non-invasive imaging.