ABSTRACT Objectives Insulinoma is a predominantly benign pancreatic neuroendocrine tumour that is traditionally managed surgically. However, surgical invasiveness and anaesthesia‐related risks limit its applicability in selected patients. Endoscopic ultrasound (EUS)‐guided ethanol ablation has emerged as a minimally invasive alternative. This study aimed to evaluate the efficacy, safety, and feasibility of EUS‐guided ethanol ablation for benign insulinoma. Methods We retrospectively analysed 17 patients with insulinoma who underwent EUS‐guided ethanol ablation, predominantly as a primary treatment. All procedures were performed by experienced gastroenterologists using 95% absolute ethanol. Results The study cohort had a mean age of 58.47 ± 12.29 years and a mean disease duration of 34.43 months (range, 0.36–84.0). Clinical success was achieved in 16 patients (94.1%). One patient with an initial suboptimal response successfully underwent a repeat ablation after 8 months. Over a median follow‐up period of 46.1 months (range, 6.6–97.8), one patient was lost to follow‐up. Disease recurrence was observed in four patients, resulting in a recurrence rate of 25% (4/16) among those with available follow‐up data. Three recurrent cases underwent repeat ablation, all achieving symptomatic resolution. A total of 22 ablation procedures were performed. Adverse events were documented in 36.4% (8/22) of procedures, with the majority being mild (31.8%, 7/22) and one severe adverse event (4.5%, 1/22). Conclusions EUS‐guided ethanol ablation is an effective and well‐tolerated treatment for benign insulinoma. It represents a viable minimally invasive alternative to surgery and remains effective for managing recurrence or initial treatment failure without compromising subsequent surgical options.
ABSTRACT Background Dopamine agonist resistance is observed in 10%–30% of patients with prolactinomas, resulting in therapeutic failure and tumour progression. The molecular mechanisms underlying this resistance are not yet fully understood, highlighting the need for the identification of novel biomarkers and therapeutic targets. Methods We performed a comprehensive integrative analysis of bulk RNA sequencing and single‐cell RNA sequencing datasets obtained from dopamine agonist‐resistant and dopamine agonist‐sensitive prolactinomas. To substantiate the primary findings, we utilised a multifaceted methodological framework that integrated Weighted Gene Co‐expression Network Analysis with machine learning techniques, including Random Forest, Support Vector Machine, and Least Absolute Shrinkage and Selection Operator. This was complemented by functional assays, which encompassed in vitro experiments involving gene overexpression and knockdown in GH3 cell models, alongside in vivo investigations using nude mouse xenograft models. Results LGALS3 has been identified as a pivotal factor in mediating resistance. Through single‐cell RNA sequencing analysis, a resistance‐specific subpopulation, termed Cluster 15, was discovered. This cluster is characterised by heightened genomic instability and stemness, as evidenced by increased expression of SOX2 and SOX9, with predominant expression of LGALS3. Mechanistically, LGALS3 activates the MAPK/ERK signalling pathway, which in turn enhances cell viability, prolactin secretion, and migration, while simultaneously inhibiting apoptosis by modulating the Bax/Bcl‐2/Caspase cascade. Functional validation studies demonstrated that silencing LGALS3 significantly reduced tumour growth both in vitro, as shown by decreased Ki67 proliferation and impaired migration, and in vivo, as indicated by reduced tumour weight and volume. Conclusion LGALS3 functions as a candidate diagnostic biomarker and represents a promising therapeutic target. Targeting the LGALS3‐MAPK axis presents a viable strategy to restore therapeutic sensitivity in patients with refractory prolactinoma.
ABSTRACT Objective Thyroid dysfunction has been increasingly reported after the coronavirus disease 2019 (COVID‐19) pandemic. To date, no population‐based study has examined this association using more than 10 million matched pairs. We compared the risk of documented thyroid outcomes after COVID‐19 with that after influenza during the Omicron‐predominant period. Methods We conducted a nationwide retrospective cohort study using the Japanese National Database of Health Insurance Claims, including patients with COVID‐19 between January 2022 and March 2023, and those with influenza between September 2017 and March 2023. Individuals with pre‐existing thyroid disease were excluded. After 1:1 propensity score matching, 24,173,646 pairs were analysed. Database‐recorded outcomes assessed within 90 days of documented COVID‐19 infection included diagnoses of thyrotoxicosis, hypothyroidism and subacute thyroiditis, as well as initiation of antithyroid drugs (ATDs) and thyroid hormone replacement therapy (THRT). Results Among database‐recorded outcomes, COVID‐19 was associated with higher risks of thyrotoxicosis diagnosis (risk ratio [RR], 1.08), hypothyroidism diagnosis (RR, 1.12), ATD initiation (RR, 1.06) and THRT initiation (RR, 1.22) than influenza, but not subacute thyroiditis diagnosis. Age‐stratified analyses showed markedly higher risks in individuals aged 0–19 years for thyrotoxicosis diagnosis (RR, 1.38) and ATD initiation (RR, 1.77). Conclusions In this nationwide cohort, COVID‐19 was associated with higher risks of database‐recorded diagnoses of thyrotoxicosis and hypothyroidism than influenza during the Omicron‐predominant period. The strongest association was observed for thyrotoxicosis diagnosis and ATD initiation in younger individuals, underscoring the importance of post–COVID‐19 thyroid monitoring in adolescents and young adults.
