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BCC represents a significant and growing public health challenge, accounting for most cutaneous malignancies worldwide. Epidemiological trends over the past decade have demonstrated a consistent rise in incidence, particularly among aging populations with a history of cumulative ultraviolet radiation exposure12,13. The external nose, serving as the central aesthetic unit of the face, is disproportionately affected, hosting a high frequency of these lesions due to its prominence and sun exposure. While Mohs micrographic surgery is widely considered the gold standard for its superior margin control and tissue preservation in high-risk areas like the nose, standard wide excision with a 5 mm margin was utilized in this specific cohort due to institutional resource availability and patient preference. Regardless of the surgical modality chosen, the resultant soft tissue defects pose a formidable reconstructive challenge14. The nose is a complex three-dimensional structure composed of distinct aesthetic subunits (tip, ala, dorsum, sidewall), and the skin in this region is uniquely sebaceous, porous, and adherent to the underlying cartilage. Consequently, reconstructing large defects requires tissue that not only fills the void but also matches the color, texture, and contour of the native nasal skin to avoid “patch-like” deformities.
Surgeons are often faced with a choice between skin grafts and local flaps. While skin grafts are technically simpler, they are prone to secondary contraction and poor color matching, often leading to alar retraction or visible scarring. Local flaps are therefore preferred for optimal aesthetic outcomes. Among the various local flap options, such as the bilobed flap, rhomboid flap, and frontonasal flap, the nasolabial fold retrograde island flap stands out as an anatomically ideal solution. It harvests tissue from the nasolabial fold, a natural reservoir of excess skin that closely mimics the quality of nasal tissue. Furthermore, the donor site can be closed primarily within the natural shadow of the nasolabial crease, rendering the post-operative scar virtually imperceptible. However, despite these aesthetic advantages, the utility of this flap has historically been limited by its vascular reliability. Unlike axial flaps supplied by a robust, named artery, the retrograde island flap relies on a subcutaneous pedicle with a reverse-flow or random-pattern blood supply. This anatomical configuration makes the flap inherently susceptible to hemodynamic instability, particularly venous congestion15.
The primary physiological hurdle in the survival of reverse-flow flaps is venous drainage, not arterial inflow. Research by Kerrigan et al. has fundamentally established that venous ischemia is significantly more deleterious to tissue survival than arterial ischemia of comparable duration16. In a retrograde flap, the pedicle must be twisted or tunneled to reach the defect. Since veins have thinner walls and lower intraluminal pressure than arteries, they are the first to collapse under mechanical torsion or external compression from post-operative edema. When venous outflow is obstructed while arterial inflow persists, hydrostatic pressure within the capillary bed rises precipitously. This triggers a cascade of pathological events: fluid extravasation into the interstitial space causes severe edema, which further compresses the microvasculature, creating a vicious cycle of congestion. At the cellular level, stasis promotes the accumulation of toxic metabolites, endothelial injury, and the activation of the coagulation cascade. Platelets aggregate in the sluggish microcirculation, leading to the formation of widespread microthrombi. Once this “no-reflow” phenomenon is established, tissue necrosis is often irreversible, regardless of subsequent interventions17,18. Therefore, the critical window for intervention is the immediate post-operative period.
Addressing venous congestion has long been a holy grail in reconstructive microsurgery. Traditional salvage strategies have included mechanical decompression (e.g., removing sutures), medicinal leech therapy (Hirudo medicinalis), and systemic pharmacological anticoagulation. Leech therapy, while effective, is associated with psychological distress for patients, prolonged bleeding, and the risk of Aeromonas hydrophila infection. Systemic anticoagulants, such as intravenous heparin or dextran, have been shown to improve microvascular patency19,20. However, the systemic administration of these potent agents carries a non-negligible risk of generalized complications, including hematoma formation, gastrointestinal bleeding, and heparin-induced thrombocytopenia. As highlighted by Boyko et al., the use of systemic anticoagulation necessitates rigorous and frequent monitoring of coagulation parameters (PT, APTT), adding to the clinical burden and cost21. Given these limitations, there is a clear clinical need for a protocol that maximizes local efficacy while minimizing systemic risks.
This study introduces a standardized protocol of immediate local micro-injection of heparin sodium, which distinguishes itself from previous methods described by Sawada et al., who utilized topical application22. This approach leverages a dual mechanism of action to ensure flap survival. Pharmacologically, injecting heparin directly into the flap tissue achieves a high local concentration of the drug exactly where it is needed in the compromised microvasculature. Heparin acts by binding to antithrombin III, accelerating the inhibition of thrombin and Factor Xa, thereby preventing the formation of fibrin clots in the sluggish venous channels. By limiting the drug to the local tissue, we avoid the systemic anticoagulation that leads to adverse events. Our safety data corroborates this: comparisons of pre- and post-operative hemoglobin, platelet counts, and coagulation times (PT, APTT) revealed no statistically significant differences, confirming that the systemic impact of this protocol is negligible. Mechanically, the multi-point puncture technique plays a crucial, often underappreciated role. The needle tracks created during injection serve as artificial drainage conduits. As observed in the results, the injection sites exhibited prolonged, controlled oozing for an average of 6 days. This “therapeutic bleeding” effectively decompresses the flap, lowering interstitial pressure and allowing arterial perfusion to continue during the critical phase of neovascularization. This concept mimics the benefits of leech therapy but in a sterile, controlled, and pharmacological manner.
For successful implementation, several critical steps and troubleshooting measures must be highlighted. The most crucial factors influencing successful outcomes are the meticulous preservation of a wide subcutaneous pedicle during dissection and the strict avoidance of pedicle kinking during the 180° rotation. If venous congestion persists or worsens despite the daily heparin injections, surgeons should troubleshoot by selectively releasing tension-bearing sutures at the recipient site to mechanically decompress the flap. If persistent stasis progresses toward necrosis, alternative salvage methods such as medicinal leech therapy may still be required. Conversely, if prolonged or excessive bleeding occurs at the puncture sites or the donor site, local heparin administration must be immediately halted, and mild, intermittent external pressure should be applied to achieve hemostasis. Beyond nasal reconstruction, the principles of this protocol may have broader clinical applications. The dual mechanism of localized pharmacological anticoagulation and mechanical decompression could potentially be adapted to salvage other high-risk random-pattern or reverse-flow flaps, such as distally based limb flaps or complex keystone flaps, where venous congestion remains a primary cause of failure.
While this protocol achieved a 100% survival rate in this cohort of 24 patients, these outcomes must be interpreted cautiously. Notably, three patients exhibited severe signs of early venous congestion (dark purple discoloration and swelling), which are typically harbingers of partial or total necrosis. In all three cases, the aggressive application of this local injection protocol successfully reversed the congestion within one week. This suggests that the window of reversibility for venous stasis can be extended by preventing local microthrombosis and facilitating drainage. Furthermore, the long-term aesthetic outcomes were excellent. The flaps maintained their bulk and texture without the atrophy often seen in skin grafts, and the donor sites healed inconspicuously. This high level of patient satisfaction underscores the value of the nasolabial flap when its vascular risks are effectively managed.
While the findings are promising, several limitations must be acknowledged. First, this was a single-center study with a relatively small sample size (n = 24). Second, the study design was a prospective case series without a randomized control group. Crucially, explicitly acknowledging the absence of a control or comparator group (e.g., a cohort receiving saline injections or needle punctures alone) limits our ability to definitively attribute the positive outcomes solely to the heparin injection protocol. It remains difficult to precisely isolate the pharmacological benefit of the antithrombotic drug from the mechanical decompression provided by the needle tracks. While historical controls and literature data suggest a higher rate of venous complications in untreated retrograde flaps, a direct comparison with a control group receiving saline injections or no treatment would provide stronger evidence of efficacy. However, ethical considerations regarding withholding potentially limb- (or nose-) saving treatment make such a design challenging. Future research could focus on comparative studies with other anticoagulants (e.g., LMWH) or determining the optimal dosage and frequency of injections through animal models23,24. Additionally, quantitative methods to assess tissue perfusion, such as laser Doppler flowmetry or indocyanine green (ICG) angiography, could provide more objective data on the hemodynamic changes induced by local heparin injections.
In conclusion, the reconstruction of nasal defects following BCC excision requires a reliable, aesthetically superior solution. The retrograde island flap of the nasolabial fold offers excellent tissue matching but is hampered by the risk of venous congestion. This study suggests that immediate, continuous local microinjection of heparin sodium provides a safe, effective, and easily reproducible method to overcome this vascular vulnerability. By combining mechanical decompression with potent local antithrombotic effects, this protocol may enhance flap survival quality, minimize systemic risks, and ensure favorable aesthetic rehabilitation for patients. This technique represents a valuable addition to the reconstructive surgeon’s armamentarium, particularly for high-risk facial flaps.