Introduction

Splenic lesions are not uncommon, but diagnosis without tissue can be difficult. Historically, ultrasound (US)-guided percutaneous splenic biopsies were associated with a 13% risk of haemorrhage [1]. Later studies have reported a much lower complication rate [2]. EUS-FNA is an alternative route for tissue acquisition. A systemic review of several small case series have shown the accuracy and safety of EUS-FNA of the spleen [3]. However, there is no direct comparison between the two methods. We present our experience, describing diagnostic efficacy and safety of both techniques.

Aims & Methods

We aim to compare the efficacy and safety of EUS-FNA of the spleen versus US-guided percutaneous biopsy. Patients who underwent EUS-FNA of the spleen from 2011-2019 and US-guided percutaneous biopsy from 2014-2019 at Addenbrooke's Hospital, Cambridge, were retrospectively reviewed. A biopsy was considered adequate when there was sufficient material obtained for histopathological diagnosis. Biopsy negative for malignancy was considered a true negative if there was stability on clinical and imaging follow-up. For non-diagnostic samples, a repeat biopsy was performed. The need for blood transfusion or therapeutic intervention was considered a major complication.

Results

Eight EUS-FNA of the spleen were done in seven patients, as one case had repeat FNA due to a non-diagnostic sample. Four of the seven subjects had focal splenic masses, one had a cystic lesion, and two had unexplained splenomegaly on CT. 22 or 25G FNA/B needles were used for focal lesions, while 19G needle was used for cystic lesion. Median (range) number of needle passes was 1.5 (1-3), with median (range) aggregate core length of 4mm (1-16). Diagnosis was established in 6 out of 7 patients (85.7%), which included three cases of diffuse large B cell lymphoma, one inclusion cyst, one extramedullary haematopoiesis, and the remaining case was negative for malignancy. Median (range) follow-up duration was 49.7 weeks (18.1-431). One patient had two non-diagnostic samples taken, and his splenic lesions were stable during the study period. There were no major complications.
Four patients had US-guided percutaneous biopsies. On CT, three patients had focal splenic lesions, and the remaining case had unexplained splenomegaly. 16-19G needles were used for biopsies. Median (range) number of punctures was 2.5 (1-3), with median (range) core length of 8mm (6-18). Three out of four patients had biopsy-proven diagnoses (75%), which include splenic Leishmaniasis, benign vascular proliferation, and the remaining was negative for malignancy. Median (range) follow-up duration was 58.1 weeks (3-242). One patient developed post-biopsy hemorrhage and required splenic artery embolization. This was complicated with myocardial infarction and acute kidney injury requiring ICU care, and he passed away 24 days later. There was one false-negative result. Biopsy from her splenic lesion did not reveal any malignancy, but PET-CT showed avid uptake (SUVmax 14.7) representing a metastasis. This was confirmed by a response to chemotherapy.

Conclusion

EUS-FNA of the spleen has comparable efficacy and is potentially safer than US-guided percutaneous approach. The choice between the two depends on the location of splenic lesions and the available expertise. Further studies are required for a more robust comparison.

References

1. Lindgren PG, Hagberg H, Eriksson B, et al. Excision biopsy of the spleen by ultrasonic guidance. Br J Radiol. 1985; 58(693): 853-7.
2. McInnes MD, Kielar AZ, Macdonald DB. Percutaneous image-guided biopsy of the spleen: systematic review and meta-analysis of the complication rate and diagnostic accuracy. Radiology. 2011; 260(3): 699-708.
3. Lisotti A, Crino SF, Mangiavillano B, et al. Diagnostic performance of endoscopic ultrasound-guided tissue acquisition of splenic lesions: systematic review with pooled analysis. Gastroenterol Rep (Oxf). 2022; 10: goac022.

Introduction

Long-term data on bowel urgency (BU) in Crohn’s disease (CD) are limited, and the associations with other efficacy outcomes are not well studied.

Aims & Methods

Our aims were to examine the long-term efficacy of mirikizumab (MIRI) on BU remission and the associations between BU remission and clinical remission, endoscopic remission, and patient-reported outcomes (PRO) improvement at week (W) 104 in patients with moderately to severely active CD who were randomized to MIRI in the Phase 3 study VIVID-1 and continued into the long-term extension study VIVID-2. In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at W0, W4, and W8, then 300 mg subcutaneously (SC) every 4W. W52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD [SES-CD]) continued MIRI SC dosing in VIVID-2. Endoscopic non-responders received reinduction with MIRI IV (3x Q4W) at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Patients that had an Urgency Numeric Rating Scale (UNRS) ≥3 (least to worst range 0-10) at baseline were included in these analyses. BU remission was defined as an UNRS score of ≤2. Associations between BU remission with clinical remission by Crohn’s Disease Activity Index (CDAI), endoscopic remission, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (range 0-52, higher is better), and Inflammatory Bowel Disease Questionnaire (IBDQ) remission, were assessed at W104, within the VIVID-1 W52 endoscopic response subgroups as well as the MIRI total group. Discontinuations or missing data were handled using modified non-responder imputation (mNRI) for categorical data. Missing values were imputed by multiple imputation and modified baseline observation carried forward for FACIT-Fatigue change from baseline.

Results

Over 50% of the MIRI total group, 56% of MIRI W52 endoscopic responders, and 43% of the MIRI W52 endoscopic non-responders achieved BU remission at W104. In the MIRI total group, a significantly higher percentage of patients achieved clinical remission, endoscopic remission and IBDQ remission at W104 in the BU remission group compared to those without BU remission. The improvement in fatigue by FACIT-Fatigue score was significantly more in the group with BU remission versus those without BU remission (p<0.0001). In both MIRI W52 endoscopic responders and non-responders, patients who achieved BU remission at W104, compared to those who did not, achieved significantly higher rates of clinical remission, greater improvements in FACIT-Fatigue, and higher rates of quality of life improvement measured by IBDQ remission (Table 1).

Table 1

Conclusion

Over 50% of patients with CD achieved BU remission at 2 years of treatment with MIRI. These results highlight that the achievement of BU remission corresponded with improvements to outcomes important to patients with CD, underscoring the importance of long-term management of BU in improving overall patient outcomes.

Disclosure

SRV: has received consulting fees, speaker’s honoraria and unrestricted research grants from Abbott, Alfasigma, Amgen, Arenapharm, BMS, Falk Pharma GmbH, Ferring Pharmaceuticals, Gilead, iQuone, Janssen, MSD, Permamed, Pfizer, Sanofi-Aventis, Schwabe Pharma, Takeda, Tillotts, UCB and Vifor
DTR: receives grants or contracts from Takeda, and discloses consultancy fees with AbbVie, Altrubio, Apex, Avalo Therapeutics, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen Pharmaceuticals, Lilly, Pfizer, Samsung Neurologica, and Takeda. He serves on the Board of Directors for Cornerstones Health.
JW, GY, AV, REM, and RRH: Employees and stockholders of Eli Lilly.
GD-H: Has received research grants from: Alimentiv BV, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and Takeda; and consulting fees from: AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, GSK, Merck Sharp & Dohme, Pfizer, Sorriso Pharmaceuticals, Takeda, Tillotts Pharma AG, and Ventyx Biosciences
ST: has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collison Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma, and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr. Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan Pharma, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Procter & Gamble, Pronota, Proximagen, Resolute Pharma, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell SA, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical
AW: reports consulting and/or speaking fees from Abbvie, Bristol-Myers Squibb, Ferring, Galapagos, Janssen, Pfizer, and Takeda.

Clinical Case Summary

Aims: We report 3 cases of new inflammatory bowel disease (IBD) which occurred in multiple sclerosis (MS) patients undergoing ocrelizumab therapy over last year in Irish Teaching Hospital setting.
Background: Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, is an established treatment for MS. While it is generally well-tolerated, emerging reports suggest a possible link to gastrointestinal complications, including IBD.
Methods: Three MS patients presented after starting ocrelizumab with gastrointestinal symptoms suggestive of inflammatory bowel disease. They were fast-tracked for endoscopic evaluation by an experienced gastroenterologist specializing in IBD. Diagnosis was based on clinical presentation, endoscopic findings, and histological analysis. Data regarding symptom onset, disease severity, colitis grade, inflammation distribution, and treatment response were assessed.
Results: A temporal relationship was observed between ocrelizumab initiation and IBD onset in all three cases, with symptoms emerging after 4-6 infusions. Reported symptoms included diarrhoea, nausea, urgency, and abdominal pain. Faecal calprotectin levels at time of referral ranged from 900 to 1800 µg/g. Endoscopy confirmed mild colitis and terminal ileitis, while histology revealed active colitis with cryptitis, acute terminal ileitis, or normal colon findings. Treatment with steroids, Mesalazine, and antibiotics led to symptom resolution in all cases. Discontinuing ocrelizumab resulted in recovery within 4-6 weeks, with no relapse over an average follow-up of two months.
Conclusion: These cases suggest a potential association between ocrelizumab and IBD onset or exacerbation in MS patients. Symptom resolution upon drug withdrawal supports a possible causal relationship. Clinicians should be aware of this risk to facilitate early detection, management, and patient education.

References

https://journals.lww.com/acgcr/Fulltext/2022/01000/Severe_Ocrelizumab_Induced_Enterocolitis_Treated.31.aspx
https://pubmed.ncbi.nlm.nih.gov/32198886/

Disclosure

No Conflict of Interest

Introduction

It is known that not all patients with eosinophilic esophagitis (EoE) in histological remission also achieve clinical remission. Several reasons have been postulated among which decreased esophageal compliance without apparent stricture at endoscopy is particularly appealing, but no data are so far available on effectiveness of empirical dilation.

Aims & Methods

Aim of our study was to investigate this topic. A retrospective analysis with prospectively collected data has been conducted on all EoE patients without stenotic features at endoscopy (i.e. no R3/S1 according to EREFS) in whom histological remission with drug and/or diet has been induced in a single referral Center from July 2018 to December 2023. All patients who had not achieved concurrent remission of dysphagia and/or bolus impaction were empirically dilated. At least 6 months of follow-up after remission was needed for inclusion. Demographic, clinical and endoscopic data were compared between patients who needed dilation and those who did not.

Results

A total of 33 patients aged 40; 30-51 yrs (median; IQR range), 23 men, were included. PPI was the main treatment (76% of pts). Nineteen of them (group 1) achieved clinico-histological whereas 14 (group 2) achieved histological remission only and underwent empirical dilation to 15-17 mm with no complications after which clinical remission was achieved in 13 of them. A second dilation was needed in 2 patients at 25 and 31 months respectively, in order to maintain remission. EREFS score at histological remission, but not at diagnosis, was higher in group 2 vs 1 (p=0.02, see table) and was accompanied by a higher % of patients with rings (R1 or R2), 78 vs 37 (p=0.04). A lower % of group 2 patients was treated with topical steroids, 7 vs 26 (p=NS).

Conclusion

In our cohort of stricture free EoE patients achieving histological remission, over 40% still had residual obstructive symptoms which were relieved by empirical esophageal dilation in most, suggesting high relevance of decreased esophageal compliance. Prospective multicenter data with use of FLIP are warranted in order to assess if topical steroids are more effective than PPIs in reversing remodeling and avoiding dilation.

References

(1) Dellon ES, Khoury P, Muir AB, Liacouras CA, Safroneeva E, Atkins D, Collins MH, Gonsalves N, Falk GW, Spergel JM, Hirano I, Chehade M, Schoepfer AM, Menard-Katcher C, Katzka DA, Bonis PA, Bredenoord AJ, Geng B, Jensen ET, Pesek RD, Feuerstadt P, Gupta SK, Lucendo AJ, Genta RM, Hiremath G, McGowan EC, Moawad FJ, Peterson KA, Rothenberg ME, Straumann A, Furuta GT, Aceves SS. A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions. Gastroenterology. 2022 Jul;163(1):59-76. doi: 10.1053/j.gastro.2022.03.025. Epub 2022 May 20.