Clinical Case Summary

A 35-year-old male presented with a one-month history of recurrent right upper abdominal pain, intermittent fever, and multifocal liver lesions. His medical history was unremarkable, besides heavy tobacco use. He denied taking any drugs or herbal medications. Initial laboratory tests showed mildly elevated inflammatory and cholestatic liver parameters. Whole-body MSCT⁽¹⁾ revealed hepatosplenomegaly and multiple, small hypodense hepatic lesions. The lungs were unremarkable in terms of malignancy. No abnormalities were found in the biliary tree, and endoscopic examination was normal. The hepatic lesion biopsy revealed an epithelioid, non-necrotic, non-caseating granuloma in the portal tract within the inflammatory infiltrate enriched with eosinophils, which were suggestive of parasitic infection or DILI. Extended workup for autoimmune liver diseases, sarcoidosis, neuroendocrine tumors, and microbial pathogens was required. Empiric antibiotic and antiparasitic therapy were initiated. All the results came negative. Three months after initial evaluation clinical symptoms persisted, in addition to new-onset dyspnea. The initial MSCT lung ⁽²⁾ scan was reevaluated and new was performed which showed bilateral thin-walled cystic lesions and small nodular opacities, predominantly in the upper lobes with no signs of progression. Based on the findings, multisystemic malignancy was suspected. A repeated pathology⁽³⁾ liver examination was positive on immunohistochemical CD1a and CD207 staining, confirming Langerhans cell histiocytosis (LCH). PET CT excluded the presence of new neoplastic foci. MRI showed no involvement of the sella turcica. The patient was referred to the Hematology Department for further evaluation and treatment management.
Hepatic involvement is a rare and under-recognized form of LCH. Liver biopsy including immunohistochemical staining with CD1a and Langerin is the cornerstone of diagnosis. Patients often receive delayed diagnosis and inappropriate treatment.

References

^1. Computed tomography (CT) scans throughout the enlarged liver showed parenchymal steatosis
and diffusely scattered, variable-sized, hypoattenuating nodular lesions with peripheral
enhancement. On magnetic resonance imaging (MRI) scans these parenchymal nodular areas
showed restricted diffusion on diffusion-weighted imaging (DWI) sequences and apparent diffusion
coefficient (ADC) map with a similar pattern of enhancement on contrast-enhanced. The findings were characteristic of intrahepatic granulomas.
^2. Chest CT displayed the bilateral presence of variable-sized, thin-walled cystic lesions (≤6 mm),
predominantly in the upper lobes, with the peripheral and subpleural distribution of small nodular
ground glass opacities (GGO) (≤2 mm).
^3. Within the portal spaces, granulomas consist of CD163-, CD1a-, and Langerin A-positive epithelioid histiocytes. Granulomas without necrosis surrounded by numerous eosinophilic granulocytes, few to moderately abundant small lymphocytes, rare pigmentophages and few neutrophilic granulocytes, and moderately abundant plasma cells (HE stain, magnification A. 100x, B. 200x; CD68 (PG -M1), CD1a, Langerin, magnification 200x).

Introduction

EUS-guided gastroenterostomy (EUS-GE) is increasingly used in the management of Gastric Outlet Obstruction. However, significant variability exists in technical choices which might account for heterogeneous clinical outcomes. The aim of this Delphi methodology was to address open questions and establish a consensus on best practices to gather expert opinions on key aspects of EUS-GE.

Aims & Methods

A panel of 25 international leading experts in EUS-GE was invited to revise literature around the technique. A Delphi process was conducted over three rounds, with each round involving anonymous voting on 29 predefined statements, using a 5-point Likert scale (1: strongly disagree – 5: totally agree). Responses were analysed through Medians [Interquartile Ranges], with pre-defined thresholds for approval, revision or discard of the statement. Statements reaching final consensus were graded based on the strength of agreement, defined as the proportion of responses rated 4 or 5.

Results

Response rate was 88% in Round 1 and 100% in Round 2 and 3. Among 29 statements, eight were approved at Round 1, eighteen at Round 2 and four at Round 3, while two were ultimately rejected.
There was early and excellent agreement (>95%) on the need of fluoroscopy for EUS-GE, the need for electrocautery-enhanced Lumen Apposing Metal Stent (LAMS), and the preference for free-hand release. All panellists agreed that endoscopists performing EUS-GE should be familiar with management of Adverse Events (AEs) such as bleedings or perforations. After discussion, excellent agreement was obtained for the management of AEs (misdeployments and bleedings) and LAMS dysfunctions.
Final Strong agreement (>90%) was reached for preferred patient positioning, the required sedation and the preference for saline solution for jejunal distention.
Extensive discussion with final Moderate agreement (>80%) was reached on the use of dye, the preference for catheter-assisted EUS-GE instead of endoscope- or needle-directed instillation, the typical location for EUS-GE and the operative space required for LAMS release.
Statements on the use of contrast and the choice between WEST and EPASS techniques were removed due to lack of agreement.

Conclusion

Despite technical differences (such as the preference of a jejunal catheter or a double-balloon catheter) most EUS-GE experts agree on key technical principles, providing valuable guidance on the standardization of EUS-GE in clinical practice. Conversely, certain topics showed limited agreement, identifying future research priorities in the field of EUS-GE.

Introduction

Biliary and gastric outlet obstruction (GOO) are common complications in patients with pancreatic cancer, often delaying essential cancer treatments. While endoscopic ultrasound-guided
gastroenterostomy (EUS-GE) has been shown to be superior to duodenal self-expandable metal stents (dSEMS) for managing GOO, the optimal strategy for biliary drainage (BD) in this setting remains unclear. Specifically, there is no consensus on whether to prefer EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided hepaticogastrostomy (EUS-HGS).

Aims & Methods

We conducted a systematic review and meta-analysis to identify the optimal biliary drainage approach in patients undergoing EUS-GE for concomitant GOO and biliary obstruction. We searched Medline, Scopus, and EMBASE up to February 2025. Studies were included if they reported outcomes of EUS-CDS or EUS-HGS in patients with biliary obstruction and concomitant GOO
treated by EUS-GE. Pooled outcomes included technical and clinical success, stent dysfunction, and adverse events, analyzed using a random-effects model. Results were reported as relative risks (RRs) with 95% confidence intervals (CIs).

Results

Five studies met inclusion criteria, comprising 128 patients (female = 45.5%; mean age range 63.0–73.0 years), with 61 undergoing EUS-CDS and 67 undergoing EUS-HGS. Four studies were conducted in Europe and one in the United States; one study was prospective. Technical success rates were similar between groups (RR 0.96, 95% CI 0.83–1.11; I² = 0%; EUS-CDS 94.5% vs EUS-HGS 96.4%), as were clinical success rates (RR 1.04, 95% CI 0.92–1.19; I² = 0%; EUS-CDS 96.5% vs EUS-HGS 89.1%). However, the risk of stent dysfunction was significantly higher in the EUS-CDS group compared to EUS-HGS (RR 4.42, 95% CI 1.71–11.43; I² = 0%; EUS-CDS 45.1% vs EUS-HGS 10.9%). The incidence of procedure-related adverse events was comparable between the two approaches (RR 1.14, 95% CI 0.24–5.50; I² = 40.8%; EUS-CDS 10.7% vs EUS-HGS 16.0%).

Conclusion

This meta-analysis suggests that both EUS-CDS and EUS-HGS are similarly safe and effective for managing malignant biliary obstruction in the setting of concomitant GOO. However, EUS-CDS is associated with a more than four-fold increase in the risk of stent dysfunction, which may result in delays to critical cancer treatments.

Disclosure

None

Introduction

Methotrexate (MTX) remains the cornerstone of treatment for rheumatoid arthritis (RA) and psoriatic arthritis (PsA), yet concerns about hepatotoxicity often lead to premature discontinuation.

Aims & Methods

This study aimed to reassess the risk of liver fibrosis in long-term methotrexate therapy and to identify clinical, metabolic, and treatment-related factors associated with hepatic changes. This was a prospective cohort study including 201 patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) undergoing MTX therapy for ≥6 months. Liver stiffness was assessed using transient elastography (Fibroscan®) and acoustic radiation force impulse (ARFI). Hepatic steatosis was evaluated using the controlled attenuation parameter (CAP). Serum-based indices (FIB-4, APRI) were calculated. Clinical and metabolic data—including BMI, waist/hip circumference, lipid profile, glucose, comorbidities, and alcohol use (B-peth)—were collected. Associations with liver parameters were analyzed using Spearman correlation and multivariable linear regression adjusted for age, sex, and diagnosis.

Results

Liver stiffness values were generally low, with minimal fibrosis detected by Fibroscan (median 4.7 kPa) and ARFI (median 2.85 kPa). ARFI and Fibroscan values showed weak but significant correlation (ρ = 0.19, p = 0.03). APRI, but not FIB-4, modestly correlated with both imaging modalities. Multivariable regression identified no independent predictors of increased liver stiffness. In contrast, CAP-measured steatosis was significantly associated with higher BMI (p = 0.002) and waist circumference (p = 0.001), while MTX dose, duration, and alcohol intake (B-peth) showed no associations. Principal component analysis confirmed that steatosis clustered with metabolic rather than pharmacologic variables.

Conclusion

In this real-world cohort, significant liver fibrosis was rare despite prolonged MTX exposure. Hepatic steatosis, rather than fibrosis, emerged as the dominant hepatic alteration, driven primarily by modifiable metabolic risk factors. These findings support the use of targeted metabolic assessment and intervention in MTX-treated patients rather than routine discontinuation based on fibrosis concern.

Introduction

Combination with an advanced therapy (AT) and immunomodulator (IMM) is commonly used to optimise outcomes in Crohn’s disease (CD) and ulcerative colitis (UC). However, the comparative benefit of IMM co-therapy with different ATs and optimal duration of IMM co-therapy are unclear.

Aims & Methods

We aimed to determine the impact of IMM co-therapy on AT persistence.
We interrogated the Persistence Australian National IBD Cohort (PANIC5) registry of CD and UC patients from 2007-2021. The PANIC registry includes 100% of AT prescribing data in Australia. Non-persistence was defined as failure to dispense prescriptions for over six months. Co-therapy with IMM was defined as concurrent dispensing of a thiopurine (azathioprine or mercaptopurine) or methotrexate during AT use. Kaplan-Meier survival curves were generated and compared using the log-rank test. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results

31,967 CD patients and 13,492 UC patients were included. 44.2% of CD and 37.9% of UC patients had received co-therapy with IMM. IMM co-therapy increased persistence of infliximab in both CD (median Kaplan Meier survival time 50.0 [95% CI 47.3-52.7] vs 27.0 months [95% CI 24.5-29.5], HR=0.68, p<0.001) and UC (35.0 [95% CI 31.4-38.6] vs 18.0 [95% CI 16.2-19.8], HR=0.71, p<0.001). Similarly, IMM co-therapy increased persistence of adalimumab in both CD (48.0 [95% CI 45.6-50.4] vs 25.0 [95% CI 23.3-26.7], HR=0.67, p<0.001) and UC (25.0 [95% CI 19.2-30.8] vs 17.0 [95% CI 14.2-19.8], HR=0.77, p<0.001). IMM co-therapy did not significantly affect persistence of vedolizumab in CD (33.0 [95% CI 27.0-39.0] vs 36.0 [95% CI 31.1-40.9], p=0.43), vedolizumab in UC (45.0 [95% CI 38.7-51.3] vs 48.0 [95% CI 41.8-54.2], p=0.11) or ustekinumab in CD (median survival and 95% CI unable to be calculated as event rate >50%; p=0.13). Ustekinumab was not approved for UC in Australia before 2021; thus no UC data were available.
Subgroup analysis showed a significant difference in anti-tumour necrosis factor inhibitor (TNFi) persistence across CD patients based on IMM timing during TNFi therapy (Table 1; p<0.001). CD patients who had at least three months of IMM before de-escalation had better persistence compared to those who stopped IMM within the first three months of TNFi (96.0 vs 19.0 months, p<0.001). Continuous IMM use during TNFi therapy had intermediate persistence (37.0 months, 95%CI 33.1-40.8). Patients who were not treated with IMM initially but started IMM in the last three months of therapy had the worst persistence (4.0 months, 95%CI 2.7-5.3). A similar pattern was seen in UC (Table 1). There was no difference between thiopurine and methotrexate co-therapy in either CD (p=0.41) or UC (p=0.45).

Table 1 – Median Kaplan Meyer persistence, stratified by timing of immunomodulator usage during anti-tumour necrosis alpha inhibitor (TNFi) therapy

Conclusion

IMM co-therapy significantly improved persistence of TNFi, but not vedolizumab or ustekinumab in both CD and UC. Discontinuing IMM within three months of commencing TNFi was associated with reduced persistence compared to continuing initial co-therapy for longer before de-escalation.

Disclosure

RWL has served as an advisory board member for AbbVie, Aspen, BMS, Celgene, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences and Takeda, and has received research funding from Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer and MRFF.

Introduction

Balanced propofol sedation administered by adequately trained non-anesthesiologist personnel has gained popularity in GI endoscopy because of its shorter procedure and recovery time, high patient satisfaction, and low rate of adverse events (AEs), even if it's still considered controversial. We reported data from a retrospective audit of Endoscopist directed nurse administered sedation (ED-NAAS) over a 2-year period in an Italian referral hospital.

Aims & Methods

Consecutive endoscopic procedures performed between October 2020 and October 2022 were considered. Under the guidance of the endoscopist, the nurse administered 1 to 2mg of midazolam, followed by a progressive top-up dosages of 10-20mg bolus of propofol to achieve moderate to deep sedation. Fentanyl was administred based on the patient's weight if indicated. Endoscopists and nurses were all certified in our hospital with a continuous and scheduled training from 2006. The patients' characteristics, dosage of administered drugs, AEs during and after the examination, were all investigated. The following AEs were deemed minor but significant: bradycardia (≤50 beats/min ≥10 seconds), hypoxia (SaO2 ≤ 90% ≥10 seconds) and hypotension (systolic BP ≤100 mmHg with a drop ≥ 20 mmHg). Major consequences included death, a persistently low state of awareness, permanent harm, the need for an emergency anaesthetist evaluation, the need for hospitalization or endotracheal intubation. To increase the sensitivity of AEs detection, reports were reviewed in these cases: (1)AEs declared in the report, (2)search by string "desaturation" "hypotension" "bradycardia" "apnoea” “hypoxia" in the report, (3)oxygen saturation level, systolic BP and heart rate ≤50 bpm annotated during the intra-procedural monitoring compared to parameters measured before sedation, (4)patients administered flumazenil, naloxone, etilephrine, atropine.

Results

A total of 19407 examinations (7803 EGDS, 10439 colonoscopies, 77 PEG, 697 EUS and 365 ERCP) and 14415 patients were enrolled. 29.4% of patients were classified as ASA I, 66.5% as ASA II and 5.1% as ASA III. Balanced sedation with propofol was administered in 86% of EGDS, 94% of colonoscopies, 92% of EUS, 94% of ERCP and in 72% of PEG. Hypotension was recorded in 1293 (6%) examination, which required fluid infusion in 330 cases (26%) and in 8 cases etilephrine to restore blood pressure. Bradycardia was recorded in 176 (0.9%) patients, which required atropine in 134 (72.8%) cases. 11 patients (0.06 %) had a minor respiratory adverse event. The mean age of patients of hypotension, bradycardia and respiratory adverse event was respectively 61.1±15 years, 64.3±15.3 and 55.6±16.2. ASA III patients were respectively 4.1%, 2.8% and 27.2% in the three groups of AEs. The mean SD/median (25^th-75^th percentil) dosage of medications were respectively 2.0±0.7mg, 2.0±0.7mg, 1.8±0.3mg of midazolam, 71.0±34.5mcg, 68.0±31.0mcg and 62.5±9.5mcg of fentanyl, 94.0±74.3mg, 77.0±61.7mg and 120 (70-190)mg of propofol. BMI and Mallampati score of II were respectively 23.0±4.5 and 72.8% in patients with respiratory AEs. 1 patient (0.001%) had a major AE, needing oro-tracheal intubation. He was 63 years old with unknown diagnosis of amyotrophic lateral sclerosis, with normal BMI, Mallampati score I, sedated with 2mg of midazolam + 80mg of propofol. Limits of the study include recall bias (missed cases of AEs not caused by sedation but because of examination itself, e.g., bradycardia or laryngospasm).

Conclusion

Balanced propofol ED-NAAS is safe in low-risk patients. Major adverse events occurred in 0.001% procedures.

Introduction

The subcutaneous (SC) formulation of infliximab offers a patient-centered alternative to the intravenous (IV) route, with the potential to improve treatment adherence, quality of life, and reduce the burden of care in patients with inflammatory bowel disease.

Aims & Methods

Aim of our study was to evaluate the clinical impact, safety, and patients’ outcomes associated with the switch from IV to SC infliximab in routine care. This was a single-center observational study incorporating both prospective and retrospective data collection. Patients with confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) who received at least two infusions of IV infliximab and subsequently transitioned to SC infliximab 120 mg every other week were eligible for inclusion. The primary endpoint was the impact of switching from IV to SC infliximab on patients' quality of life and work productivity measured through the SF-36 and WPAI-GH questionnaires administered at baseline and at week 52. Secondary endpoints included safety profile and clinical effectiveness, defined as clinical remission or improvement at weeks 8, 24 and 52 following the switch to SC infliximab.

Results

A total of 109 adult patients (72 UC (66,1%), 64 male (58.7%)) were enrolled. Median age was 41.6 ± 12.2 years. The switch from IV to SC infliximab was associated with an improvement in work productivity in both UC and CD at week 52 in terms of absenteeism (p = 0.04; η² = 0.18; 95% CI: 0.03–1.00 in CD and p < 0.001; η² = 0.25 in UC) and productivity loss (p < 0.001; η² = 0.47; 95% CI: 0.34–1.00 in CD and p < 0.001; η² = 0.30 in UC) . No significant differences were found in activity impairment, presenteeism, or across SF-36 domains in either CD or UC cohorts (all p > 0.05). Transitioning from IV to SC infliximab did not affect patients’ perceived quality of life as assessed by physical, mental, or social functioning scores. At week 52, 51 out of 55 (93%) patients with UC and 20 out of 27 (74%) patients with CD were in clinical remission. Switching from IV to SC infliximab was significantly associated with achievement of clinical remission over time in UC (χ² = 8.83, p = 0.03 with Cramér’s V = 0.16). In patients with CD, switching from IV to SC infliximab did not show a statistically significant association with the achievement or maintenance of clinical remission at months 12 (χ² = 1.02, p = 0.80 with Cramér’s V = 0.00; 95% CI: 0.00–0.13). The switch was well tolerated with no new safety issues. In total, 6 patients experienced mild adverse events (erythema in the injection site in 3 patients, urinary tract infection in 1 patient, allergic reaction in 1 patient, and skin rash in 1 patient), leading to treatment discontinuation in 3 cases. No patient suffered from severe adverse events.

Conclusion

Switching from IV to SC infliximab is associated with significant improvements in work productivity at week 52 in both UC and CD. No new safety issues were found. These findings support the SC formulation of infliximab as a safe and effective option in the management of inflammatory bowel disease.

Disclosure

G Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion. LPeyrin‐Biroulet declares personal fees from Galapagos, AbbVie,Janssen,Genentech,Ferring,Tillots,Celltrion,Takeda,Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS,Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, PandionTherapeutics,GossamerBio,Viatris, ThermoFisher.Grants fromAbbvie,MSD, Takeda, FreseniusKabi. Stockoptions:CTMA. S Danese has served as a speaker, consultant and advisory board member for Schering‐Plough, AbbVie, MSD, UCB Pharma, Ferring, Cellerix, MilleniumTakeda, Nycomed, Pharma cosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, NovoNordisk, Cosmo Pharmaceuticals, Vifor and Johnson&Johnson, NikkisoEuropeGMBH, Theravance