Current evidence of experimental and clinical studies on freezing nitrogen ethanol composite in bone tumor surgery.

BACKGROUND: Local recurrence after surgical resection of bone tumors remains a major challenge. Liquid nitrogen (LN) cryotherapy is a widely used adjuvant but carries risks of spillage, fracture, and soft tissue injury. Freezing Nitrogen Ethanol Composite (FNEC), a semisolid mixture of LN and ethanol, has been proposed as a safer alternative with comparable tumoricidal effect. This scoping review aimed to synthesize experimental and clinical evidence on the efficacy and safety of FNEC in bone tumor surgery. METHODS: A scoping review was conducted per PRISMA-ScR guidelines, searching MEDLINE (via PubMed), Cochrane, Google Scholar, Semantic Scholar, Dimensions, Aminer, and OpenAlex through May 2026. Experimental (ex vivo, in vivo) and clinical studies (cohorts, case series, case reports) evaluating FNEC in bone tumors were eligible. Data were synthesized narratively. RESULTS: Of 166 records screened, 7 studies were included (1 experimental, 1 mixed, 5 clinical; 118 patients). Both experimental studies showed FNEC achieved tumoricidal efficacy comparable to LN (97.6% vs 90.4% bone shrinkage, p = 0.008) while causing less apoptosis in bone, muscle, and skin (15%-35% less tissue damage), and sustaining a lethal -122°C isotherm at 10-mm depth where LN's efficacy fell sharply (8.3% vs 100% stromal cell death at 5 mm). Across the clinical studies, no recurrence occurred in 4 studies (one did not report recurrence), and one cohort study recorded a 12.5% recurrence rate with 90.6% five-year recurrence-free survival. Perioperative complications were infrequent, ranging to 6.4%, and exclusively superficial; no study reported neurovascular injury. CONCLUSIONS: Clinicians can consider FNEC a lower-morbidity adjuvant alternative to LN in select cases, but should interpret this evidence cautiously. Every clinical study is observational, uncontrolled, and concentrated in a small number of Asia-Pacific institutions, with FNEC protocols unstandardized. Further research should prioritize multicenter randomized trials with standardized FNEC protocols and validated outcome instruments.