Introduction

Balloon dilation and plastic stent deployment have been performed as hepaticojejunostomy stricture (HJS) treatment techniques by PTBD or under DB-ERCP guidance. Although these techniques have shown favorable clinical results, the treatment period can be long because stent deployment is required. In addition, HJS may recur even after treatment because the scar tissue itself remains. To overcome these challenges, we developed an transluminal antegrade piecemeal dilation technique (TAPD) for treating HJS. The aim of this study was to evaluate the technical feasibility and safety of this technique in terms of the pre- and post-cholangioscopic findings.

Aims & Methods

This retrospective study included consecutive patients who were complicated with symptomatic HJS between November and February 2022. The primary outcome of this study was the technical success rate of TAPD using a drill dilator. Technical success was defined as resolution of the HJS, based on the cholangioscopic findings. The secondary outcome was adverse events associated with TAPD such as bleeding or perforation.

Results

TAPD was attempted at around 11 days after EUS-HGS in 19 patients. Among the 19 patients, passage of the guidewire across the HJS into the intestine was unsuccessful in 4 patients, and the technical success rate of this procedure was 78.9%. TAPD was successful in all 15 patients in whom passage of the guidewire was achieved. After TAPD, cholangioscopy identified no bleeding or perforation in any patient. During the follow-up period, no recurrence of HJS was observed in any patient who underwent TAPD.

Conclusion

In conclusion, TAPD appears to be technically feasible and safe. Although it is necessary to conduct a randomized trial in comparison with other methods, with long-term follow up, TAPD may be a useful option for the treatment of HJS.

Introduction

Acute pancreatitis (AP) is one of the most common and widely increasing gastrointestinal diseases leading to hospitalization without specifically available therapy [1]. It is mainly caused by gallstones, possibly by increasing the pressure in pancreatic duct with refluxing of bile acids (BAs) or changing of serum BA concentration due to bile duct obstruction [2]. So far, few existing reports only mentioned total BA measurements without considering their hydrophilic potential. Our data from experimental work showed that systemic BAs can modulate severity of AP depending on their hydrophobicity and the involvement of cholecystokinin [3]. As a further translational step, we aimed to investigate the role of systemic BAs profiles and analysed their association with the etiology and severity of AP in human.

Aims & Methods

Serum from AP patients and a healthy control group was collected and stored at -80⁰C. A profile of 20 different BAs was quantified by liquid chromatography tandem mass spectrometry-based assay using the AbsoluteIDQBAs kit according to the manufacturer’s instruction. The workflow was managed by MetIDQ and the data was analyzed by Oracle database XE software. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated for each patient at the first and third day of hospitalization and were compared by subtraction of the values (Δ APACHE II). Diagnosis criteria and severity of pancreatitis were assessed according to the Revised Atlanta classification and the APACHE II score.

Results

There were 214 AP patients with mean age of 60±16 (range 26-87) years and 50.4 % were female. Biliary origin was diagnosed in 133 (62.1%) patients and non-biliary pancreatitis (mainly alcoholic AP) in 81 (37.9 %) cases. In non-biliary AP, profiles of both hydrophobic and hydrophilic BAs did not differ from controls. In biliary AP, significantly elevated levels were detected for hydrophobic BAs but not hydrophilic one. The total concentrations of hydrophobic BAs were 33.86±4.51 μM in biliary AP and 8.068±1.98 μM in non-biliary AP (p < 0.0001). Cut-off values were 0.30 μM and 3.78 μM for hydrophilic and hydrophobic BAs, respectively. The total amount of hydrophilic BAs was not different between the groups of deteriorated (Δ APACHE II >0) and ameliorated or stable AP (Δ APACHE II ≤ 0). Conversely, total hydrophobic BAs concentrations were significantly higher in the worsened AP (55.8±12.3 μM) group than in those who recovered or at least did not deteriorate (5.9±0.6 μM). However, ursodeoxycholic acid (UDCA), a hydrophilic BA, was significantly decreased in severe disease and showed a reduced trend in moderately severe AP.
Hydrophobic BAs had more predictive potential with an area under the curve (AUC) of 0.762, a sensitivity of 83.75% and a specificity of 60% at the cut-off value 11.84 μM, whereas hydrophilic BAs were only of limited use for the prediction of AP deterioration, as AUC was 0.57 with a sensitivity of 65% and a specificity of 44% at the cut-off 0.7 μM. Additionally, UDCA concentrations of less than 19 nM can be used to distinguish biliary AP from non-biliary AP with an AUC of 0.723, sensitivity 75%, and specificity 65%. For detection of deterioration, UDCA alone with cut-off concentration 18 nM showed a value with an AUC of 0.68, sensitivity 76%, and specificity 61%.

Conclusion

In patients, the sum of hydrophobic but not total hydrophilic BAs associated with the etiology and severity of AP. Serum levels of UDCA, a particular type of hydrophilic BAs, inversely associated with the severity of AP, which suggests a protective role.

References

[1]. Iannuzzi, J.P.; King, J.A.; Leong, J.H.; Quan, J.; Windsor, J.W.; Tanyingoh, D.; Coward, S.; Forbes, N.; Heitman, S.J.; Shaheen, A.A.; et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology 2022, 162, 122-134, doi:10.1053/j.gastro.2021.09.043
[2]. Lerch, M.M.; Aghdassi, A.A. The role of bile acids in gallstone-induced pancreatitis. Gastroenterology 2010, 138, 429-433, doi:10.1053/j.gastro.2009.12.012
[3]. Tran, Q.T.; Sendler, M.; Wiese, M.L.; Doller, J.; Zierke, L.; Gischke, M.; Glaubitz, J.; Tran, V.H.; Lalk, M.; Bornscheuer, U.T.; Weiss F.U; Lerch, M.M and Aghdassi A.A. Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis. International journal of molecular sciences 2022, 23, 13592. doi: 10.3390/ijms232113592

Disclosure

The authors declared no Conflict of Interest.

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

Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to an uncontrolled immune response orchestrated through, i.e. neutrophils. The basement membrane acts as a front-line defense promoting tissue integrity, where the α-3 chain of type IV collagen is solely expressed on the outermost layer of the mucosa. Detection of subclinical ulceration is crucial since early-stage IBD presents a unique window of opportunity for intervention, as the disease might become a self-sustaining process once deep inflammation becomes established. We therefore, wanted to develop a biomarker reflecting early tissue injury, aiding in the implementation of prompt treatment.

Aims & Methods

A competitive enzyme-linked immunosorbent assay quantifying a human neutrophil elastase (HNE) degraded fragment of type IV collagen α-3 chain was developed (C4A3-HNE). Dilution- and spiking recovery, inter- and intra-variability, and interference were evaluated. Acceptance criteria for technical validation were a recovery of 100% ±25 and an inter-intra variability of <15%. Commercial serum samples were purchased from ProteoGenex. Biological relevance was validated in an observational study from Odense University Hospital (OUH) and healthy controls. Groups were compared using Kruskal Wallis (Dunn‘s corrected).

Results

The technical validation of the C4A3-HNE assay demonstrated acceptable results for recovery, variation, and interference. Biological relevance was assessed in commercial IBD samples and healthy donors. C4A3-HNE was elevated in both CD and UC compared to healthy (p=0.001 and <0.0001)(AUC [95% CI]: 0.820 [0.669-0.971]; 0.875 [0.775-1.000]). The results were validated in an independent cohort of IBD patients (both p<0.0001). For UC, analysis showed that compared to patients in endoscopic remission, C4A3-HNE is elevated in patients with mild endoscopic activity, decreasing dose-dependently for moderate and severe disease (T1). Fecal calprotectin and CRP levels were also lower in IBD patients with high levels of C4A3-HNE (T1). With a cut-off value of 54.1 ng/ml, C4A3-HNE could significantly discriminate between mild and severe endoscopic disease (T1).

Conclusion

Our study demonstrates the biological and possible clinical relevance of the novel C4A3-HNE biomarker. The biomarker is elevated in patients with IBD compared with healthy, and high levels may reflect early mucosal damage in patients with UC. Furthermore, inflammatory markers were lower in IBD patients with high levels of C4A3-HNE, pointing towards high levels being indicative of early disease. C4A3-HNE may provide early detection of mucosal damage or prediction of relapse; however, further studies are required to assess the clinical validity of this biomarker.

Disclosure

MA, MP, MK, and JM are employees of Nordic Bioscience A/S. MK owns stocks in Nordic Bioscience A/S.

Introduction

Despite new therapeutic strategies, substantial proportion of patients with ulcerative colitis (UC) undergo colectomy at some point. Restorative proctocolectomy with ileal pouch ano anastomosis (IPAA) is regarded as intervention of choice in these patients. However, the disease conversion to Crohn´s disease (CD) is reported in up to one third of these patients who necessitate immune suppressive treatment after IPAA. Considering the life-long need for immune suppressive therapy in these patients, ileo-rectal anastomosis (IRA) would represent a good alternative to IPAA in this specific group of patients. Todate, no data are available to predict the UC-CD conversion. One of the possibility to reduce the risk of performing IPAA in patients developing CD in pouch is to use the modified two-stage proctocolectomy approach and identify patients who develop CD endoscopically between colectomy and the restoration of continuity.

Aims & Methods

The aim of the present study was to assess the UC-CD conversion rate identified prior IPAA via ileoscopy.
All patients with UC operated in one tertiary IBD center between 2016 and 2021 were identified in medical records. The main outcome was CD detected at ileoscopy between the first stage operation, i.e. total colectomy with terminal ileostomy and the restoration of continuity either via IPAA or IRA. The ileoscopy was performed between three to six months after colectomy. The secondary outcome was the rate of conversion to CD after IPAA or IRA.

Results

Sixty patients underwent total colectomy (mean age 41 years, range 22-77; 62% were men); seven patients were lost to follow-up, finally the data from 53 patients were analysed. The majority of these patients (36 - 68%) underwent colectomy for therapy resistent chronically active UC, 9 (17%) patients for acute severe UC, 2 patients had benign colonic stenosis, 5 had high-grade dysplasia or colorectal cancer detected at surveillance colonoscopy and one patient had extensive pseudopolyposis.
All resection specimen were reviewed and no histopathological features of CD were found. Three out of the 53 (6%) ileoscopically assessed patients prior IPAA or IRA were diagnosed with CD in prestomal terminal ileum. During the further follow-up, additional 4 patients developped CD, two after IPAA, one with definitive ileostomy in prestomal ileum and one in neoterminal ileum after IRA.
In total 7 out of 53 patients in this cohort developped CD (13%). Using the two stage approach with ileoscopy between colectomy and restoration of continuity, three out of these seven patients with CD convertion in this cohort were detected prior the decision on the type of second-stage operation.

Conclusion

The conversion from ulcerative colitis to Crohn`s disease occurs in a significant proportion of IBD patients after colectomy. Ileoscopy performed between the two stages of restorative proctolectomy is helpfull in detecting these patients and guiding the decision on the type of surgical intervention to restore continuity.

Disclosure

Nothing to disclose.

Introduction

Long-term outcomes of gastric subepithelial lesions have not been elucidated. To reveal the natural history, we initiated a prospective, 10-year follow-up of patients with small (≤20 mm) gastric subepithelial lesions in September 2014. Here, we report the results of an interim analysis of a prospective observational study.

Aims & Methods

In total, 567 patients with 609 lesions were prospectively registered between September 2014 and August 2016. The location, size, morphology, and number of subepithelial lesions were recorded on a web-based case report form.

Results

The endoscopic follow-up period was 4.60 ± 1.73 years (mean ± SD), and survival data were investigated for 5.28 ± 1.68 years. This interim analysis revealed that the estimated cumulative incidence of a size increase ≥5 mm, after accounting for patients’ death and resection of the tumor as competing risk events, was 4.5%. In addition, the estimated cumulative incidence of lesion size increase ≥5 mm or resection of lesions was 7.7% at 5 years, and that of size increase ≥10 mm or resection of lesions was 4.3% at 5 years.

Conclusion

These results indicate that approximately one in 13 patients with small (≤20 mm) gastric subepithelial lesions may require resection or further investigation for increased tumor size (≥5 mm) within five years under active surveillance.

References

Nishida T, Hirota S, Yanagisawa A et al. Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version. Int J Clin Oncol 2008; 13: 416-30.

Disclosure

This study has been conducted as an Academic Committee Working Group of the Japan Gastroenterological Endoscopy Society.