Introduction

Use of antithrombotics including antiplatelet agents and anticoagulants is associated with upper and lower GI bleeding, thus a higher rate of positive findings is reasonable to be expected when patients receiving these drugs undergo SBCE for the investigation of SBB. However, the results of published studies concerning the impact of antithrombotics on the SBCE diagnostic yield remain conflicting. Furthermore, the clinical outcome of patients under antithrombotics who undergo SBCE for the investigation of SBB is not currently known.

Aims & Methods

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). Multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient’s bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode.

Results

During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) patients receiving antithrombotics, compared to 1113/5866 (18.9%) not receiving these drugs (p<0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occured in 927 (36.5%) of patients receiving antithrombotics (36.5%), compared to 795 (13.5%) not receiving these drugs (13.5%, p<0.00001).

Conclusion

Both the diagnostic yield of SBCE and the rebleeding rate were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real world setting only in a minority of patients with positive findings.

References

1. Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol 2015; 66: 2271–2281.
2. Abraham NS, Hlatky MA, Antman EM, et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of PPI and thienopyridines: focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Am J Gastroenterol 2010; 105:2533–2549.
3. Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal anti-infammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol. 2007;5:1040–1045.
4. Nagata N, Niikura R, Yamada A, et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS ONE. 2016;11:e0151332.
5. Lepileur L, Dray X, Antonietti M, et al. Factors associated with diagnosis of obscure gastrointestinal bleeding by video capsule enteroscopy. Clin Gastroenterol Hepatol. 2012;10:1376–1380.
6. Shiotani A, Honda K, Murao T, et al. Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury. Scand J Gastroenterol. 2011;46:281–286.

Introduction

Acute pancreatitis is the most common and serious complication of endoscopic retrograde cholangiopancreatography (ERCP). Risk factors for PEP are classified as patient-related and endoscopist- or technique- related factors. However, patient-related factors focused on the pancreatic volume and intrapancreatic fat content have not been investigated previously. In this study, we used 3- dimensional (3D) volumetry, and histogram investigated the potential association of pancreatic head volume and fat content with the incidence of PEP.

Aims & Methods

We retrospectively analyzed 157 patients who underwent ERCP for diagnostic or therapeutic purposes.Pancreatic volume was measured by using contrast-enhanced images obtained by continuous 5.0-mm, 320-, 64-row detector CT before ERCP. Computed tomography scan images of precontrast and venous phase were used for evaluation. Pancreatic volume was determined by using 3D analysis software. The pancreas was divided into the head and body/tail using the left edge of the superior mesenteric-portal vein confluence, and the volume of each part was calculated separately. Hounsfield unit histogram analysis (HUHA) was performed by using precontrast images. The percentage of HUHA ≤0 Hounsfield unit (HU) in pancreatic parenchyma represented the fat content. Multivariate analysis was performed to identify risk factors for PEP.

Results

PEP occurred in 35 patients (PEP group) and the incident rate was 22.3%. The mean volume of the whole pancreas was significantly larger in the PEP group (p<0.001). The mean volume of the pancreatic head was significantly larger in the PEP group (p<0.0001), but there were no significant differences in those of the pancreatic body and tail. Fat content of the pancreatic head was significantly higher in the PEP group (p<0.01), but there were no significant differences in fat content of the pancreatic body and tail. Multivariate analysis revealed that the pancreatic guidewire placement (hazard ratio [HR], 4.7; p < 0.01), the pancreatic head volume (HR, 7.1; p < 0.01), and fat content of the pancreatic head (HR, 5.1; p < 0.01) were independent risk factors for PEP.

Conclusion

The volume and fat content of the pancreatic head were independent predicting factors for PEP. Quantitative assessment of the pancreas using multislice CT imaging may contribute to the prediction of the onset of PEP.

Introduction

It is sometimes difficult to distinguish between autoimmune pancreatitis (AIP) and pancreatic neoplasm. In imaging diagnostic examination, long or multiple strictures, or segmental/focal narrowing of pancreatic duct without marked upstream dilatation in endoscopic retrograde pancreatography is important finding to diagnose as AIP. It has been speculated that the narrowing of pancreatic duct is attributed to periductal lymphoplasmacytic infiltration characteristic of histology in AIP. We reported a resected case of AIP in which branch pancreatic duct wall thickening demonstrated by endoscopic ultrasound (EUS) reflected periductal lymphoplasmacytic infiltration¹⁾. EUS that provides high resolution image of pancreas can delineate periductal lymphoplasmacytic infiltration as pancreatic duct wall thickening.

Aims & Methods

The aim of this study is to determine whether pancreatic duct wall thickening on EUS contributes to the diagnosis of AIP. From March 2017, when we began focusing on pancreatic duct wall thickening in AIP, to March 2023, there were 24 consecutive patients diagnosed with AIP in our department. EUS was performed in all of them, and the presence of pancreatic duct wall thickening was noted on the EUS report. Pancreatic duct wall thickening was focused on a thickened wall with symmetry, irregular luminal caliber, and a smooth hyperechoic layer covering the surface¹⁾. The international consensus diagnostic criteria for AIP were applied. The detection rate of pancreatic duct wall thickening on EUS, characteristics according to pancreatic duct wall thickening, and the change of pancreatic duct wall thickening after steroid therapy were investigated.

Results

All patients were diagnosed with type 1 AIP (definitive type 19, probable type 2). Median age was 70 years (range: 55-82), and male was 18 patients. The median serum IgG4 level at diagnosis was 446 mg/dL (range: 147-2600). The detection rate of pancreatic duct wall thickening on EUS was 83.3% (20/24). Localization was diffuse in 12 patients and segmental/focal type in 12 patients. Other organ involvement was observed in 13 patients. There was no difference in the above factors depending on the presence or absence of pancreatic duct wall thickening. Twenty patients underwent steroid trial. Among them, 7 patients who underwent EUS after steroid trial showed improvement in pancreatic duct wall thickening.

Conclusion

Pancreatic duct wall thickening on EUS was often seen in patients with AIP and improved with steroid therapy. Focusing on this imaging finding may be useful in the diagnosis of AIP.

References

1. Ishii K, Hisa T, Shiozawa S, et al. A resected case of focal autoimmune pancreatitis with pancreatic duct wall thickening representing periductal lymphoplasmacytic infiltrate. Clin J Gastroenterol 2021; 14: 1278-1285.

Introduction

Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and for the treatment of relapsing multiple sclerosis (RMS). Ozanimod is a first-in-class S1P receptor modulator approved for UC, and one of several S1P receptor modulators used for the treatment of RMS. Ozanimod has been extensively studied in RMS with large patient populations and long exposure times, which can provide more insight into the safety profile of ozanimod in UC.

Aims & Methods

This analysis evaluated the tolerability and safety of long-term ozanimod 0.92 mg/day treatment from clinical trial data in adults with moderately to severely active UC and from clinical trial data in adults with RMS. The UC population included patients pooled from phase 2 (NCT01647516), phase 3 (NCT02435992), and respective open-label extension (OLE; NCT02531126) trials through January 10, 2022. The RMS population included patients treated with ozanimod 0.92 mg in DAYBREAK (NCT02576717; October 16, 2015–February 1, 2022), an ongoing OLE trial of patients from phase 1‒3 ozanimod studies. Safety outcomes included treatment-emergent adverse events (TEAEs) and TEAEs of special interest based on association with S1P modulation. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated to adjust for time on study.

Results

Mean (SD) ozanimod exposure in 1158 patients with UC was 28.4 (23.3) months (2714.9 total PY exposure); ozanimod exposure in 2494 patients with RMS was 56.4 (15.9) months (11,732.2 PY; UC and MS combined: 14,447.1 PY). TEAEs occurred in 74.6% of UC and 88.2% of RMS patients. Serious TEAEs were reported in 17.3% of UC and 14.1% of RMS patients, and TEAEs leading to ozanimod discontinuation in 9.3% and 3.6%, respectively. The most common TEAEs were lymphopenia (12.3%; EAIR 5.6/100 PY), anemia (8.4%; EAIR 3.7/100 PY), lymphocyte count decreased (7.9%; EAIR 3.5/100 PY), and nasopharyngitis (7.9%; EAIR 3.5/100 PY) in patients with UC, and nasopharyngitis (20.6%; EAIR 5.1/100 PY), headache (16.9%; EAIR 4.0/100 PY), and upper respiratory infection (11.9%; EAIR 2.7/100 PY) in patients with RMS. In UC and MS, respectively, EAIR/100 PY were 20.2 and 22.9 for any infection, 1.6 and 0.8 for serious infection, 1.2 and 1.4 for opportunistic infection, and 0.6 and 0.3 for malignancy. Alanine aminotransferase levels ≥5 times the upper limit of normal occurred in 2.3% and 0.8% of UC and RMS patients, respectively.

Conclusion

Long-term ozanimod 0.92 mg/day was generally well tolerated and safe for most patients with moderately to severely active UC or RMS.

Disclosure

SD: received honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor.
BACC: received personal compensation for consulting for Alexion, Atara, Autobahn Therapeutics, Avotres, Biogen, EMD Serono, Gossamer Bio, Horizon Therapeutics, Neuron23, Novartis, Sanofi, TG Therapeutics, and Therini Bio; and received research support from Genentech.
DCW: received research honoraria as a speaker, consultant, and/or advisory board member from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Pfizer, and Takeda.
OA: received honoraria as a speaker from Janssen, Pfizer, and Takeda.
LC, AP, JKS, CYC, JVR, and DS: employees and/or shareholders of Bristol Myers Squibb.
FDL: participated in consulting agreements, advisory boards, and/or data and safety monitoring boards with Acorda, Actelion, Apitope, Atara, Biogen, BrainStorm Cell Therapeutics, EMD Serono, GW Pharmaceuticals, Immunic, Innate Immunotherapeutics, Jazz Pharmaceuticals, Mapi Pharma, MedDay, MedImmune/Viela Bio, Mylan, Novartis, Orion Biotechnology, Polpharma, Population Council, Receptos/Celgene, Roche/Genentech, Sanofi/Genzyme, Teva, and TG Therapeutics.
JAC: received personal compensation for consulting from Biogen, Bristol Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and Pharmaceutical Security Institute; speaking from H3 Communication; and serving as an editor of Multiple Sclerosis Journal.
DTR: received grant support from Takeda; served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Takeda, and TechLab.

This study was sponsored and funded by Bristol Myers Squibb.