Introduction

Intraductal radiofrequency ablation (RFA) has been proposed as an adjunctive therapeutic method for patients with inoperable perihilar
cholangiocarcinoma(pCCA). Because there is limited data regarding the benefits of RFA, we aimed to evaluate the feasibility, efficacy and safety of a RFA based endoscopic palliation protocol.

Aims & Methods

Consecutive inoperable patients presenting biliary obstruction secondary to pCCA were evaluated according to the ongoing, single center, randomized clinical trial(NCT05563870). Native-papilla patients were randomized 1:1 to biliary drainage of the viable liver territories with plastic stents (control) or drainage plus RFA of the entire length of the tumor (active arm). Following index procedure, patients were scheduled for stent exchange and additional RFA treatment (active arm only) at 8-10 weeks intervals. Primary outcome was clinical efficacy defined as bilirubin levels < 3mg/dL at 4 weeks after index ERCP; secondary outcomes included overall survival and safety outcomes.

Results

Heretofore we included 25 patients (13 active arm) undergoing 72 procedures (37 with RFA) for a median follow-up of 3 months (range 2-15). Most patients received either 2 (10/25) or 3 (3/25) plastic stents at index ERCP and 23/25 of the patients reached effective drainage at 4 weeks, only 7 patients receiving undelayed oncologic treatment. There were 11 deaths during follow-up - 6 unrelated to the cholangiocarcinoma, 3 from therapy-related complications and 2 from cancer progression. 20/25 patients experienced at least 1 adverse event - including 15 severe biliary events with no significant differences between the study groups.

Conclusion

Extensive liver drainage followed by iterative stent exchange with intraductal RFA applications seems feasible and effective in the
palliation of biliary obstruction in pCCA patients, with no additional risk related to RFA applications. However, adverse events related to biliary infection remain a frequent and life-threatening occurrence during follow-up in this patient population. Further data on the optimal timing and RFA application protocol is required.

Disclosure

No conflict of interest

Introduction

The PROFILE trial in patients with newly-diagnosed Crohn’s disease demonstrated that “top-down” therapy, with combination infliximab and immunomodulator from diagnosis, provided superior efficacy and a better safety profile over a one-year follow-up period compared to a conventional “accelerated step-up” management approach.

Aims & Methods

The current study aimed to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication (intravenous infliximab, subcutaneous infliximab, subcutaneous adalimumab) as soon as possible after diagnosis. A de novo Markov model was developed to model the cost-effectiveness of using a “top-down” compared to “accelerated step-up” strategy in adults newly-diagnosed with active Crohn’s disease (HBI score >7, elevated CRP and/or faecal calprotectin >200ug/g and endoscopic evidence of disease activity with simple endoscopic score of Crohn’s disease activity of >6 [>4 if ileal-only disease]). Parameters were informed by individual patient data from PROFILE and data from the published literature. Use of intravenous infliximab, or subcutaneous infliximab, or subcutaneous adalimumab from diagnosis were modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 18 PROFILE trial sites in 2024. Key model outcomes included healthcare costs (drug acquisition, drug administration, disease management, hospitalisation, surgery) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results

The base case cost-effectiveness analysis indicated that a “top-down” strategy dominated over an “accelerated step-up” approach. Initiating intravenous infliximab from diagnosis yielded greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and was less costly, saving £1,681 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of SC infliximab and adalimumab. The greatest cost savings were with adalimumab, totalling £10,059 per patient over 5 years. Sensitivity analyses further supported the robustness of the results for “top-down” therapy, showing it to be the most cost-effective option in 98.7% of model simulations.

Conclusion

This health economic analysis demonstrates that early effective “top-down” treatment with anti-TNF therapy from diagnosis results in lower healthcare resource use compared to an “accelerated step-up” strategy. The economic benefits align with improved clinical outcomes, as early, effective treatment better controls inflammation. Patients experience longer periods in remission, fewer disease-related flares, and enhanced quality of life. These findings were demonstrated for intravenous infliximab, subcutaneous infliximab and subcutaneous adalimumab. In newly-diagnosed patients with active Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-effective than “accelerated step-up” based treatment strategies.

References

Noor NM, Lee JC, Bond S et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427.

Disclosure

NMN declares educational/travel grants and/or speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda and Tillotts Pharma AG.

Introduction

Acute-on-chronic liver failure ( ACLF) is a severe form of acute decompensation of chronic liver disease with a high short-term mortality rate. It is characterized by excessive systemic inflammatory response and extrahepatic multiorgan failures (1). Previously published data have shown that therapeutic plasma exchange (TPE) decreases mortality rate in patients with ACLF reducing cytokine levels, serum bilirubin, and coagulopathy (2,3).

Aims & Methods

This retrospective study was conducted at the University Clinical Center of Serbia. All patients diagnosed with ACLF according to the EASL criteria and treated with TPE from January 2021 to January 2024 were included. (1) The main indication for providing TPE was serum bilirubin level >12 mg/dl with no improvement to standard medical treatment (SMT). The following scores were calculated at the hospital admission: Model for end-stage liver disease (MELD), Model for end-stage liver disease-Sodium (MELD-Na), Chronic Liver Failure Consortium- acute-on-chronic liver failure (CLIF-C ACLF). All patients were followed for 90 days. MELD and MELD-Na scores were calculated as well on the day 28.
The aims of this study were: assessment of 28-day and 90-day survival in patients with ACLF, the impact of TPE on MELD, and MELD-Na score.

Results

The study included 40 patients in whom SMT did not lead to improvement, of which 32 (80%) were male and 8 (20%) were female with a median age of 45.5 ( 39.75-58.5) years. The most frequent cause of liver cirrhosis was alcohol ( n=28; 70%), followed by Wilson disease (n=4; 10%), metabolic dysfunction-associated fatty liver disease ( MAFLD) (n=3; 7,5%), autoimmune hepatitis ( n=2; 5%), primary biliary cholangitis ( n=2; %%), AIH/ PSC syndrome overlap (n=1; 2.5%). Eighteen patients (45%) were previously diagnosed with acute decompensation ( Table 1). The average number of performed TPEs was 6±12.73. In alcohol-related liver disease (ALD) cirrhosis, alcoholic hepatitis was the main cause of ACLF in 22 (78.5%) patients. Twenty-two patients (55%) were diagnosed with Community-acquired infections. At admission, the average MELD and MELD-Na scores were 28.5±6.43 and 31±6.21. The mean MELD and MELD-Na scores in surviving patients after 28 days were 24.3 ±7.78 and 25.52±7.58, respectively. The average CLIF C-ACLF score at admission was 47±8.07. ACLF grade 1 was observed in 20 patients (50%), ACLF grade 2 in 18, (45%), and ACLF grade 3 in 2 (5%). The 28-day mortality in this study group was 37.5% (n=15), with 25% (n=5) in ACLF grade 1, 44.4%(n=8) in ACLF grade 2, and 100% (n=2) in ACLF grade 3. Ninety-day mortality was 62.5% (n=25). Regarding the ACLF grade, the following 90-day mortality was observed: grade 1-45%( n=9), grade 2-77.8%( n=14), and grade 3-100 (n=2). With the use of TPE in addition to SMT, a statistically significant decrease in MELD and MELD-Na as well was observed after 28 days (p <0.01).

Conclusion

TPE may be a beneficial treatment option for patients who do not respond to SMT, but in our study, short-term mortality is still high. New prospective randomized studies with a larger number of subjects are needed to examine this therapeutic modality accurately.

References

1. European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on acute-on-chronic liver failure. Journal of Hepatology, 79(2), 461–491.
2. Mao WL, Chen Y, Chen YM, Li LJ. Changes of serum cytokine levels in patients with acute on chronic liver failure treated by plasma exchange. J Clin Gastroenterol. 2011;45:551–555.
3. Chris-Olaiya A, Kapoor A, Ricci KS, Lindenmeyer CC. Therapeutic plasma exchange in liver failure. World J Hepatol. 2021;13(8):904-915.

Disclosure

There is no conflict of interest.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/