OBJECTIVE: To evaluate the reliability of liquid nitrogen freezing for the treatment of lip mucosal hemangioma in infants and young children. METHODS: Sixty-three infants and young children were diagnosed with lip mucosal hemangioma and treated with liquid nitrogen freezing, among them, 20 were males and 43 were females, aged 3 to 18 months, with a mean age of 3.5 months. The tumors were mainly concentrated in 3 sites, 19 cases in the upper lip, 40 cases in the lower lip, and 4 cases in the corners of the mouth. Pre-operative, post-operative and each follow-up, photographic records were taken. The treatment results were evaluated at a follow-up of 8 to 14 months. Results: 77.8% of patients were completely effective, 15.9% were significantly effective, and 6.3% were partially effective. No serious complications were observed in all cases. CONCLUSION: Liquid nitrogen cryotherapy for lip mucosal hemangioma is safe, effective, and reliable. As a common disease in infants and children, the incidence of hemangioma is 1%-2%, and the oral and maxillofacial area accounts for more than 70%, while the lip mucosa is a more common site for the growth of this tumor, accounting for about 20.9% of the oral and maxillofacial area. The tumors often appear in the neonatal period, either congenitally or within a few days to weeks after birth. 2 to 3 months later, they start to enter the proliferative phase, and then grow rapidly and faster than the body’s development. Infants and children with hemangiomas located in the trunk and extremities still have time to be observed, while those growing in the five senses, especially the mouth and lips, should not wait to be observed. Tumor growth is particularly rapid during this period, and the small size and fine structure of the child’s mouth and lips make it difficult to recover surgically once the tissue structures such as the lip crest, lip beads, and human body are destroyed [3]. Currently, there are many treatment methods for lip hemangioma, including drug therapy, laser therapy, radiation therapy, and surgical revision. We used liquid nitrogen freezing method to treat 63 cases of lip mucosal hemangioma in infants and children, and achieved good results, which proved that the method is safe and effective. 1.Surgical method After admission, patients were given relevant examinations, and contraindications were excluded, and the operation was performed in the operating room under inhalation anesthesia. A metal head of the same size and shape as the tumor lesion area was selected (metal head is a kind of freezing tool made by forging a steel spoon. The head was pancake shaped, 1.5 cm × 1.5 cm × 0.2 cm, Figure 1). The surgical area was routinely disinfected with Anl iodine (III), and the autoclaved metal head was immersed in liquid nitrogen for 1.5 min, removed, and quickly placed on the lesion and pressed firmly. At this time, the frozen lacrimal mucosa tumor area was frosted, white and slightly hard; the ablation time was about 3 min, and the operated area became soft and swollen after rewarming. The freezing range is 0.5 cm beyond the tumor. 2 to 3 freeze-thaw cycles (1 freeze-thaw cycle = 1 freezing time + 1 ablation time) are required for 1 freezing treatment. The treatment effect can be achieved in about 3 cycles. If the metal head is smaller than the lesion area, multi-point freezing should be done. Oral or intravenous medication is generally not required after surgery. 2.Evaluation criteria Pre-operative, post-operative and each follow-up examination are given the same body photo records, and finally the initial admission photo is taken for comparison with the follow-up examination photo 1 month after the completion of the last treatment, and the tumor size, mucosal color and lip shape indexes are used as the evaluation basis for the efficacy. According to the evaluation criteria of hemangioma treatment developed by Chen et al. A volume reduction of 25% to 50%, moderate mucous membrane coloration, and moderate deformity of lip shape were considered generally effective; a volume reduction of <25% and no improvement of lip mucous membrane color and shape were considered ineffective. There were no anesthetic complications in this group of patients. 2 patients developed ulcers and blood oozing from the surgical area due to excessive freezing intensity, and were treated with local drug changes and discharged in about 1 week. 63 patients were followed up for 8 to 14 months, with an average of 10 months. Among them, 49 cases (77.8%) were completely effective, 10 cases (15.9%) were apparently effective, 4 cases (6.3%) were partially effective, none were ineffective or generally effective, and the two patients who developed ulcers and oozing blood also achieved partial effectiveness. Scar crusting was seen in the early postoperative period and slowly softened, leaving very little scarring. In the 1960s, Cooper invented the use of liquid nitrogen for local tissue freezing and used cryotherapy in surgical practice. Most scholars now believe that the mechanism of tumor cell destruction by cryogenic freezing are ①Ice crystal theory: Mazur et al. believe that rapid cooling leads to the formation of a large number of intracellular ice crystals, thus affecting the proliferation ability of cells. popken et al. believe that during the rewarming phase, when the temperature reaches above -400C, the cell membrane is damaged, permeability increases, and cells and subcellular structures expand and rupture. ②Microvascular thrombosis theory: Liu Zibo et al. confirmed in animal experiments that freezing caused vascular endothelial cell damage and sustained smooth muscle spasm, leading to microvascular intravascular thrombosis and prompting tumor apoptosis. ③Immunological effects: In l967, Yantorno C et al. confirmed the existence of freezing immune response. Cryopreservation induces an inflammatory response and massive leukocyte infiltration, which induces an immune response. Zhang et al. examined the changes of peripheral blood T lymphocyte subsets and serum immunoglobulins in 10 lung cancer patients at different periods before and after surgery, and the results showed that after cryopreservation, CD3 , CD4 , and CD4/CD8 ratios increased significantly compared with those before surgery, while CDT8 decreased significantly and immunoglobulins also increased significantly. TUNEL staining showed that necrotic tissue was in the center of the frozen foci, and positive cells mainly accumulated in the frozen peripheral area, which morphologically had apoptotic cell characteristics. The number of TUNEL-positive cells in the frozen group was significantly higher than that in the control group. 5, analysis of cryotherapy techniques At present, cryotherapy is widely used clinically, such as cryotherapy for liver cancer, colorectal cancer, cervical and vaginal vault acromegaly, vitiligo, etc. The study of Ding Hongcai et al. concluded that oral mucosa freezing is completely different from the skin freezing situation. After mucosal freezing, the necrotic tissues separate and fall off quickly, and it is not easy to form thick scabs, much less dry scabs. Wound healing is rapid, and the structural alteration of the submucosal tissue is completed in 3-4 weeks. After reviewing the literature, Mao Tienqiu et al. concluded that the damage to capillaries was the most serious after freezing. During the freezing process, the freezing intensity is greatest in the center and edge of the frozen body (metal head) and spreads in a cone shape to the deeper part, and the intensity gradually decreases beyond 6 mm from the center of freezing, and the intensity is negligible. Therefore, the treatment method described in this paper is only applicable to hemangiomas located in the mucosa, limited in scope and superficial. According to our clinical studies, cryotherapy of lip mucosal hemangiomas is effective and complications such as ulceration, erosion, and infection rarely occur. To prevent these complications, the following points need to be noted during the procedure: ① Avoid "overdoing it". On the one hand, the metal head should not be placed on the tumor with violent pressure, and the force should be controlled to avoid extrusion injury; on the other hand, we should not be worried about extrusion injury and "slapdash". ②Control of freezing intensity. The choice of freezing intensity is based on the size, location and estimated depth of the tumor. For small and shallow tumors, the freezing time should be shortened, but should be at least 1 min or more. After freezing, the area should show swelling or small blisters. The presence of oozing blood and large blisters indicates that the freezing intensity is too large and too deep. ③ Due to the presence of saliva, sudden cooling can cause the lip to adhere to the metal head, and with gradual rewarming, the metal head will separate from the lip mucosa, and the metal head must not be pulled forcibly to avoid bleeding and traumatic ulceration and secondary infection. ④This operation is also a kind of surgery, the principle of asepsis must be strictly observed, the operation area is routinely disinfected, and the freezing device should be disinfected at high temperature. ⑤ The high temperature and hyperthermia inevitably accompanying the operation area after freezing will speed up the evaporation of the mucosal surface of the affected area, causing dryness of the mucosa and easily causing chancre. The local use of tetracycline eye ointment can play a moisturizing role on the one hand, and prevent the occurrence of infection on the other. At present, the effect of surgical resection and repair of lip hemangioma is not yet satisfactory. On the one hand, it is difficult to find matching tissues due to the peculiarities of the lip mucosa; on the other hand, the scar left by the surgery not only affects the aesthetics, but also may affect the development of the jaw bone. Early surgery is generally not advocated if the hemangioma is not a fatal growth or in cases that cannot be cured by non-surgical intervention. Radiotherapy has been abandoned because of its uncertain efficacy and serious complications. Shock therapy within 6 months of corticosteroid application is generally free of adverse effects, although some adverse effects such as excitement, polyuria, polycholism, thrush and gastrointestinal reactions have been reported. The occurrence of edema, ulceration, and scarring with cryotherapy has also been reported rarely. narrow indications for treatment (for mucosal hemangioma, not for body surface skin hemangioma) are the main problems of this technique, which requires a stepwise improvement and innovation in treatment methods. chen et al. applied this technique to treat 127 patients with lip mucosal hemangioma and achieved satisfactory results. Based on the results of our study, 77.8% of the patients were completely effective and 15.9% were significantly effective without serious complications, indicating that liquid nitrogen freezing is a safe and effective method for treating superficial lip mucosal hemangioma in infants and children, and that liquid nitrogen is convenient to obtain and inexpensive, which makes it easy to promote its application.