赫尔辛基大学中心医院

OBJECTIVE:To compare high ligation and stripping (HLS), endovenous laser ablation (EVLA), and ultrasound guided foam sclerotherapy (UGFS) for symptomatic great saphenous vein (GSV) reflux in the long term, given the limited comparative data beyond ten years. METHODS:Patients with symptomatic GSV reflux were randomised (1:1:1) to undergo HLS, EVLA, or UGFS. One hundred and ninety-six patients treated at Helsinki University Hospital were invited to 14 year follow up. Primary outcomes were above knee GSV reflux and GSV re-intervention rates. Secondary outcomes included quality of life. RESULTS:Of 233 randomised patients, 214 were included. UGFS increased the risk of GSV reflux recurrence compared with both HLS (risk ratio [RR] 11.7, 95% confidence interval [CI] 1.6 - 85.6) and EVLA (RR 5.0, 95% CI 1.5 - 16.6; 30.8% [12 of 39] after UGFS vs. 2.6% [one of 38] and 6.1% [three of 49] after HLS and EVLA, respectively; overall p < .001). UGFS was associated with a higher risk of GSV re-interventions compared with HLS (RR 4.3, 95% CI 1.8 - 10.2) and EVLA (RR 6.9, 95% CI 2.6 - 18.4; 56.4% for UGFS vs. 13.2% for HLS and 8.2% for EVLA; overall p < .001). Neovascularisation rates did not differ between the treatments (29.0%, 22.5%, and 23.1% for HLS, EVLA, and UGFS, respectively; overall p = .76). Aberdeen Varicose Vein Questionnaire scores were comparable across the groups (median [interquartile range] 8.9 [3.7, 13.3] in HLS, 6.1 [0.8, 12.2] in EVLA, and 8.8 [4.1, 13.4] in UGFS, with median differences of +2.8 [HLS vs. EVLA], +0.1 [HLS vs. UGFS], and -2.7 [EVLA vs. UGFS]; overall p = .21). CONCLUSION:UGFS demonstrated inferior outcomes in terms of GSV recurrent reflux and re-intervention rates compared with both HLS and EVLA, whereas HLS and EVLA showed comparable performance across these outcomes. Long term quality of life was comparable across all groups.

Background Oncolytic adenoviruses are immunotherapeutic agents that selectively replicate in malignant cells, inducing direct oncolysis, and reshaping the tumor microenvironment. While neutralizing antibodies (nAbs) are known to limit viral vector efficacy, emerging evidence suggests they may also have a role in improving clinical outcomes. This study investigates the kinetics, composition, and functional roles of nAbs, and association with overall survival and response rate in patients treated with TILT-123 (igrelimogene litadenorepvec), an Ad5/3 oncolytic adenovirus encoding tumor necrosis factor and interleukin-2.Methods Multiple serum samples from 58 patients enrolled in three TILT-123 phase I clinical trials (NCT04695327, NCT04217473, NCT05271318) were analyzed for anti-TILT-123 nAbs using a cell-based functional neutralization assay. ELISA was used to quantify IgM, IgA, and IgG targeting TILT-123. Functional antibody signaling studies included antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis (ADCP) assays. Serum proteomics, peripheral blood mononuclear cell (PBMC) profiling, and tumor immunofluorescence/RNA-seq were used to immunologically contextualize nAb induction. Survival was evaluated by Kaplan-Meier analysis, and responses by RECIST v1.1. Biomarker assessment for clinical benefit was evaluated using confusion matrices.Results Cross-trial analysis demonstrated induction of nAb titers against TILT-123. Patients achieving high neutralizing titers early on-treatment (days 8–22) had longer survival (median OS 280 vs 190 days) and higher response rates. Baseline anti-TILT-123 IgG and IgM levels correlated with prolonged OS. ADCP activity on day 36 was associated with improved survival and disease control. Integrated serum, PBMC, and tumor IF/RNA-seq analyses supported humoral immune remodeling and increased immune trafficking and identified lymphotoxin-α as a systemic driver of early nAb induction. Early on-treatment high nAb titers emerged as the strongest single biomarker of clinical benefit, while combinatorial analyses suggested that incorporating additional factors, such as baseline nAb titers or lymphotoxin-α levels, may enhance biomarker suitability.Conclusions High early on-treatment anti-TILT-123 nAb titers were associated with improved clinical outcomes, while ADCP activity and a pro-humoral systemic milieu supported functional roles beyond viral neutralization. These findings identify nAbs and antiviral humoral immunity as candidate biomarkers and potential effector mechanisms in oncolytic virus therapy development.

Aims:Surgical management of intermediate and malignant tumours in the pelvis is complex. Complications are frequent and either related to the surgery itself or to post-surgical failure of the reconstruction technique. This systematic review and meta-analysis aims at analyzing all reported complications following PI to PIII pelvic resections for intermediate and malignant tumours. Methods:Based on a systematic literature search on PubMed adhering to the PRISMA guidelines, 1,683 study records were identified, of which we included 90 original studies published until 22 July 2025. Overall complication rates were assessed with random-effects meta-analysis. Differences in complication rates between reconstruction types (i.e. megaprosthetic, mostly biological, none) were evaluated with meta regression analysis. Results:Data on 2,199 patients (1,250 males (57%)) with mainly PI to PIII pelvic resections were analyzed. The most common reconstruction types were custom-made implants (21%; n = 451) and ice-cream cone prostheses (14%; n = 312). Pooled rates of infections, wound healing problems, nerve injuries, and deep vein thrombosis (DVT) amounted to 15% (95% CI 12% to 18%), 13% (95% CI 10% to 15%), 7% (95% CI 5% to 9%), and 4% (95% CI 2% to 6%), respectively. Further, pooled implant revision/removal and secondary external hemipelvectomy rates were 14% (95% CI 11% to 17%) and 4% (95% CI 3% to 5%). Mostly biological reconstructions were associated with higher rates of nerve injuries (p < 0.001), construct failures (p = 0.010), and secondary implant revision/removal (p = 0.003) compared to megaprosthetic reconstruction. Further, biological reconstructions were associated with increased secondary external hemipelvectomy rates compared to megaprosthetic reconstructions (p = 0.005) or no reconstructions (p = 0.001). Conclusion:Treatment of pelvic malignancies is challenging, with technically demanding resections and complex reconstructions. Across all reconstruction techniques following sacrum-sparing pelvic resections, infections and wound healing problems are the most common complications, yet there is also a considerable proportion of patients with neurovascular complications and DVTs.