Ross, Sharona

Background: Splanchnic venous thrombosis (SVT) is a potentially severe and frequently underdiagnosed complication following splenectomy in patients with hematologic diseases. Despite its clinical importance, no standardized, evidence-based guidelines currently exist to inform perioperative prevention, diagnosis, or treatment in this population. Materials and Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines to estimate the incidence and risk factors for SVT after splenectomy in patients with hematologic diseases. Twenty-eight observational studies comprising 5025 patients were included. Risk factor data were analyzed using random-effects models. In parallel, an international Delphi consensus process was performed involving 35 experts (hematologists and surgeons) from 14 countries. Experts were assigned to five domain-specific groups and developed clinical statements on prophylaxis, diagnosis, and management of SVT. Consensus was defined as ≥80% agreement, and recommendations were graded using the GRADE framework. Results: The pooled incidence of SVT after splenectomy was 11.4%, with higher rates in studies using routine imaging (20.7%) and those conducted at single centers (15.1%). Splenic size and weight were significant risk factors, while age, BMI, and platelet count were not. Disease-specific risk was highest in patients with myeloproliferative neoplasms, lymphoma, and thalassemia. The Delphi process generated 25 consensus statements, 14 of which were classified as strong recommendations. Key guidance included perioperative vaccination, individualized thromboprophylaxis with BMI-adjusted low molecular weight heparin, selective Doppler-based screening in high-risk patients, and stepwise anticoagulation regimens based on thrombus burden and clinical evolution. Conclusion: This study presents the first international consensus-based guidelines for managing SVT after splenectomy in patients with hematologic disease. Developed through systematic evidence synthesis and expert consensus, these recommendations provide a practical framework rather than definitive standards of care and support individualized prevention, detection, and treatment strategies in this high-risk population.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.