Noriko Aramaki-Hattori

Background/Objectives: Slow-flow vascular malformations, including venous malformation (VM), lymphatic malformation (LM), and Klippel–Trenaunay syndrome (KTS), are rare, symptomatic disorders with limited treatment options. This study evaluated the efficacy and safety of serabelisib, an orally available selective phosphoinositide 3-kinase α inhibitor, in these patients. Methods: This phase 3, multicenter, single-arm, confirmatory study was conducted in Japan (September 2023–June 2025). Patients aged ≥2 years received oral serabelisib once daily (100 mg for body weight ≥ 40 kg; 60 mg/m² for p < 0.001) and remained significant in post hoc sensitivity analyses for null rates of up to 16%. Response rates were 19.0% (VM), 33.3% (LM), and 50.0% (KTS). Quality of life did not improve consistently. Adverse drug reactions (ADRs) occurred in 52.8% of patients (grade 3 or 4, 22.2%), most commonly hyperinsulinemia (13.9%), nausea (11.1%), and liver function test abnormal (11.1%); most hepatic ADRs (13 of 15 events) resolved after dose interruption or discontinuation. One death (tubulointerstitial nephritis) was judged unrelated to treatment. Conclusions: Serabelisib produced radiological responses exceeding a natural history benchmark in refractory VM, LM, and KTS, with hepatic toxicity requiring monitoring. Larger controlled studies with longer follow-up are needed to confirm its clinical benefit and long-term safety.

Background/Objectives: The therapeutic efficacy of percutaneous sclerotherapy (PS) for venous malformations (VMs) based on volumetric magnetic resonance imaging (MRI) measurements and its association with early post-treatment coagulation markers remains unexplored. This study evaluates the therapeutic efficacy of 5% monoethanolamine oleate (EO)-based PS in treating difficult-to-resect VMs using volumetric MRI and investigates its association with early changes in coagulation markers. Methods: This post-hoc analysis utilized data from a prospective, open-label, multicenter clinical trial initiated on 1 January 2021. The correlation between MRI-determined volume reduction and post-sclerotherapy changes in coagulation markers was assessed. Results: Between January 2021 and April 2023, 44 patients underwent EO-based PS. Based on a ≥ 20% VM volume reduction, patients were classified into “achieved” (n = 26; 59.1%) and “non-achieved” (n = 18; 40.9%) groups. D-dimer levels significantly increased on postoperative day 1 (POD1) compared with pretreatment screening (p < 0.001), whereas fibrinogen and prothrombin international normalized ratio levels remained unchanged. In the achieved group, a significant correlation was observed between the volume reduction rate and the administered EO dose per lesion volume (mL/cm³; Spearman’s ρ = 0.43, p = 0.03). The non-achieved group showed significantly higher D-dimer elevation than the achieved group (p = 0.03). Conclusions: This is the first multicenter study to evaluate EO-based PS efficacy for VMs using volumetric MRI and explore its relationship with early post-treatment coagulation markers. Elevated D-dimer levels on POD1 were not predictive of treatment efficacy, highlighting their limited clinical utility in assessing therapeutic response.

Unlike adults, early developing fetuses can completely regenerate tissue, and replicating this could lead to the development of treatments to reduce scarring. Mice epidermal structures, including wound healing patterns, are regenerated until embryonic day (E) 13, leaving visible scars thereafter. These patterns require actin cable formation at the epithelial wound margin through AMP-activated protein kinase (AMPK) activation. We aimed to investigate whether the administration of compound 13 (C13), a recently discovered AMPK activator, to the wound could reproduce this actin remodeling and skin regeneration pattern through its AMPK activating effect. The C13 administration resulted in partial formations of actin cables, which would normally result in scarring, and scar reduction during the healing of full-layer skin defects that occurred in E14 and E15 fetuses. Furthermore, C13 was found to cause AMPK activation in these embryonic mouse epidermal cells. Along with AMPK activation, Rac1 signaling, which is involved in leaflet pseudopodia formation and cell migration, was suppressed in C13-treated wounds, indicating that C13 inhibits epidermal cell migration. This suggests that actin may be mobilized by C13 for cable formation. Administration of C13 to wounds may achieve wound healing similar to regenerative wound healing patterns and may be a potential candidate for new treatments to heal scars.

Mast cells and inflammatory cells are abundant in keloid and hypertrophic scar tissues. Even if the cause of physical injury is similar, such as piercing or scratching with hands, clinical findings show differences in the size of keloids in the same area. Hence, we performed histological studies on giant keloids larger than the earlobe, and other smaller keloids. We also examined the risk factors associated with the formation of giant lesions. No statistically significant differences in the association of the risk factors were observed. However, histological observations clearly showed a high number of degranulated or active mast cells with a trend towards a greater number of degranulated mast cells in the giant keloid tissues. Collagen production also tended to increase. Two patients with giant keloids were severely obese, suggesting that the persistent inflammatory state of obesity may also be involved in the growth of keloid lesions.

Background: The current standard treatment for keloids is a combination of surgery and postoperative radiotherapy with 8–25 Gy. Case presentation: Our case was a 75-year-old patient who developed a swollen mass in her chest 20 years after excision of a chest keloid followed by 32 Gy postoperative radiotherapy. After resection of the swollen mass, pathology indicated extraskeletal osteosarcoma. Conclusions: Six putative cases of carcinogenesis after postsurgical radiotherapy for keloid have been reported over the last 70 years. To our knowledge, this is the first case of post-keloid radiotherapy carcinogenesis that meets the definition of a radiation-induced sarcoma. The risk of secondary carcinogenesis after postsurgical radiotherapy for keloid is small but must be explained to the patient.