Introduction

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. The median survival after resection is about 60 months. However, when regional lymph node (LN) metastases are found, survival drops to only 20 months. Survival for patients with extraregional LN involvement (i.e., stage IV disease) is even worse. These patients may benefit from preoperative or palliative treatment rather than upfront surgery. Recently, the European Association for the Study of the Liver (EASL) and International Liver Cancer Association (ILCA) clinical practice guidelines advocated the use of endoscopic ultrasound (EUS) with tissue acquisition (TA) of LN for presumed resectable iCCA patients, if a positive LN would alter management. The aim of this study was to evaluate the yield of EUS with TA of LN in presumed resectable iCCA patients and to determine its impact on clinical decision making.

Aims & Methods

In this retrospective, multicentre cohort study, patients with potentially resectable iCCA who underwent preoperative EUS from 2010-2020 were included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to positive LN found with EUS-TA. Extraregional LN (e.g., aortocaval and celiac trunc) were distinguished from regional LN. EUS was not performed in a standardized manner and TA was performed at the discretion of the endosonographist.

Results

A total of 56 patients were included. The EUS reports described 71 LN (29 regional; 42 extraregional) in 46 patients (82%). EUS-TA was performed of 55 LN, with a yield (i.e., malignancy confirmed) in 21 LN of 19 patients (35%). Fifteen patients (27%) had positive extraregional LN. Surgical exploration was precluded due to positive LN in 17 patients (30%). Fifteen patients (27%) did not undergo surgical exploration for other reasons, such as tumour progression. The remaining 24 patients (43%) underwent surgical exploration of whom 8 (33.3%) underwent a resection, after a median period of 1.5 months. Five patients (21%) had positive LN at surgical exploration that were not detected at EUS, including 2 patients with extraregional LN.

Table 1. Baseline characteristics of the included patients

Conclusion

Preoperative EUS in patients with resectable iCCA had a yield of 35% of patients with TA-confirmed positive LN. In 30% of patients the multidisciplinary team and the patient decided to withhold surgery because of positive LN. The ongoing POELH trial (NCT05678218) prospectively investigates standardized preoperative LN assessment.

Disclosure

R.P. Voermans is a consultant for and receives grants for investigator-initiated studies from Boston Scientific. M.J. Bruno serves as a consultant and receives support for industry and investigator-initiated studies from Boston Scientific and Cook Medical and receives support for investigator-initiated studies from Pentax Medical, 3 M, Interscope, and Mylan. The other authors declare that they have no conflicts of interest.

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

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.

Clinical Case Summary

Colorectal lymphomas are a rare cause of colonic neoplasia (0.2-0.6% malignant neoplasms of large bowel). Approximately 10% are primary colorectal lymphomas, while the rest correspond to colonic extension of systemic lymphoproliferative diseases.
We present the case of a 66-year-old woman with a history of rectum and pancreas adenocarcinoma (both in remission). During a follow-up CT, a thickening of the cecal pole was identified, with no adenopathy or other relevant findings (Photo1). The patient had no abdominal pain or B symptoms (night sweats, weight loss or fever).
The diagnosis was completed with a PET-CT that showed pathological uptake in the cecum (Photo2), so a colonoscopy was performed, which revealed a large polypoid lesion (30 mm) at the ileocecal level, with nodular areas with small ulcerations and no clear loss of the glandular pattern (Photo 3), from which multiple biopsies were taken.
Biopsies showed lymphoid proliferation with a ‘starry sky’ pattern, mitosis and apoptosis, and positive immunohistochemistry for CD45, CD20, CD10, BCL6, BCL2 and C-MYC, together with a high proliferation index (Ki-67 > 95%), all compatible with high-grade B-lymphoproliferative syndrome with Burkitt morphology (Photo 4).
Burkitt's lymphoma is a rare B-cell lymphoma (15% of GI lymphomas), associated with chromosomal translocation (8:14, 8:22 and 2:8) and overexpression of c-myc oncogene.
There are three clinical variants: endemic (common in Africa and associated with EBV and malaria), HIV-associated and sporadic (20%).
It is common in children and its most frequent symptoms are abdominal pain and weight loss, so diagnosis is often delayed. Although the yield of endoscopic biopsies is low (<20%), it is a key tool in its diagnosis, along with targeted biopsy of abdominal adenopathies.
Despite its aggressiveness, treatment with targeted chemotherapy achieves rates of more than 90%, and early diagnosis is essential to avoid complications and ensure adequate medical treatment.

References

- Photo 1: Thickening of the cecal pole seen in CT-Scan.
- Photo 2: Pathological uptake in the caecal area as seen on PET-CT Scan.
- Photo 3: Polypoid lesion in ileocecal area at colonoscopy
- Photo 4: Pathological anatomy of endoscopic biopsies: starry sky imaging and immunohistochemistry of Bcl-2 and C-myc