OBJECTIVE In a previous study, the authors showed that the migration of Schwann cells (SCs) through end-to-side (ETS) neurorrhaphy promotes axonal regrowth within an acellular nerve graft. In the present study, the authors investigated whether a similar strategy using an artificial nerve (AN) would allow reconstruction of a long nerve gap (20 mm) in rats. METHODS Forty-eight 8- to 12-week-old Sprague Dawley rats were divided into control (AN) and experimental (SC migration-induced AN [SCiAN]) groups. Prior to the experiment, the ANs used in the SCiAN group were populated in vivo with SCs over a 4-week period by ETS neurorrhaphy onto the sciatic nerve. In both groups, a 20-mm sciatic nerve defect was reconstructed in an end-to-end fashion using 20-mm ANs. Sections from the nerve graft and distal sciatic nerve in both groups underwent assessments at 4 weeks for SC migration by immunohistochemical analysis and quantitative reverse transcription–polymerase chain reaction. At 16 weeks, axonal elongation was assessed by immunohistochemical analysis, histomorphometry, and electron microscopy. The number of myelinated fibers was counted, the g-ratio was calculated, and myelin sheath thickness and axon diameter were measured. Furthermore, functional recovery was evaluated at 16 weeks using the Von Frey filament test for sensory recovery and by calculating the muscle fiber area for motor recovery. RESULTS The area occupied by SCs at 4 weeks and by axons at 16 weeks was significantly larger in the SCiAN group than in the AN group. Histomorphometric evaluation of the distal sciatic nerve revealed a significantly greater number of axons. At 16 weeks, plantar perception in the SCiAN group was significantly better, demonstrating improvement in sensory function. However, no tibialis anterior muscle motor improvement was observed in either group. CONCLUSIONS The induction of SC migration into an AN by ETS neurorrhaphy is a useful technique for repairing 20-mm nerve defects in rats, with better nerve regeneration and sensory recovery. No motor recovery was observed in either group; however, motor recovery might require a longer period of time than the lifespan of the AN used in this study. Future studies should investigate whether structural and material reinforcement of the AN, to lower its decomposition rate, can improve functional recovery.

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 <40 kg) for up to 52 weeks. The primary endpoint was the response rate at the final evaluation (≥24 weeks), defined as the proportion of patients achieving a ≥20% reduction from baseline in target lesion volume on blinded, centrally reviewed magnetic resonance imaging. The response rate was compared with a natural history-based null rate of 6.7% (exact binomial test). Trial registration: jRCT2041230064. Results: Thirty-six patients received serabelisib. The response rate was 30.6% (11/36; 95% confidence interval, 16.3–48.1%; 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.

Background: Total pelvic exenteration (TPE) creates a massive pelvic dead space associated with a high risk of severe postoperative complications. We evaluated the clinical outcomes of pelvic floor and perineal reconstruction using a modified posterior thigh flap including the gluteus maximus muscle in patients undergoing TPE for anal canal cancer. Patients and Methods: We retrospectively reviewed 4 male patients who underwent this reconstruction at our institution between April 2020 and March 2025. Clinical outcomes, including operative details, postoperative complications, and ambulatory function (assessed through manual muscle testing), were analyzed. Results: All flaps survived completely, effectively obliterating the pelvic dead space. No major complications, such as pelvic sepsis, fistula formation, or ambulatory dysfunction, were observed at 6 months postoperatively. Hip extension strength on the reconstructed side was preserved at manual muscle testing grade 5 in all patients. Minor donor-site complications consisted of one hematoma requiring surgical hemostasis and 2 minor wound dehiscences that healed with conservative management. Conclusions: The posterior thigh flap, including the gluteus maximus, provides ample vascularized tissue to fill the pelvic cavity, spares the abdominal wall, and allows for early mobilization. In addition, releasing the muscle insertion provides greater flap mobility. This technique is a reliable reconstructive option that may minimize postoperative morbidity following TPE.