Scars can be physiological or pathological and are left on the skin after wound healing. Pathological scars protrude from the skin surface and may cause discomfort [1, 2]. Keloids are a type of pathological scar that grows beyond the original wound area and does not naturally regress. They have invasive growth and can affect appearance, function, and quality of life. The formation of keloids is complex and may be related to multiple factors. Treatment methods are diverse, but keloids are prone to recurrence. Surgical treatment is effective but has a high recurrence rate. Postoperative electron beam therapy can reduce the recurrence rate with minimal side effects [3]. This study investigated the incidence pattern of keloids and factors affecting the efficacy of postoperative electron beam therapy by analyzing 66 patients with 133 keloids.

Patients and Methods

This study analyzed 66 patients diagnosed with hypertrophic scars who underwent surgical treatment combined with postoperative local electron beam therapy at a hospital from January 2015 to May 2021. Among them, 43 patients were followed up, and the treatment outcomes of 39 patients were statistically analyzed to explore the characteristics of hypertrophic scars and the impact of factors such as gender, age, etiology, location, symptoms, and the start time of electron beam therapy on treatment efficacy. The inclusion criteria were as follows: (1) clinical diagnosis of hypertrophic scars and postoperative pathological diagnosis of hypertrophic scars; (2) surgical excision followed by direct suture or local flap transfer repair; (3) postoperative electron beam therapy at the hospital radiotherapy center. The exclusion criteria were (1) incomplete data and (2) age less than 16 years old.

A treatment plan for keloids was designed based on location, size, and tissue tension. Keloids were completely removed at the superficial fascia layer. Different surgical methods were used to close the wound depending on its size. If the keloid was large, a one-stage expander was implanted, and a two-stage keloid excision and expanded skin flap transfer repair were performed. After the operation, patients were promptly consulted by the radiotherapy department and signed an informed consent form for radiotherapy, and a radiotherapy plan was formulated. Depending on the patient’s acceptance of the radiotherapy method, 8–9 MeV electron beams generated by the Swedish Elekta Infinity linear accelerator were used. The starting time of postoperative radiotherapy varies from immediate to 5 days after surgery. During irradiation, the dressing was removed, and a 0.5-cm-thick dose compensator was added. The irradiation range was 5–10 mm from the edge of the incision, and the depth was 2.0 cm subcutaneously. Attention was paid to protecting normal tissues and skin in the surgical area, and any adverse reactions were observed. If there were serious adverse reactions, the treatment was immediately stopped. The dressing in the surgical area was changed after each radiotherapy session, and the wound was re-disinfected and dressed. Please refer to Fig. 1 in this study for details on removing keloids during surgery.

Fig. 1
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Surgical procedure—A preoperative, B intraoperative, C immediate postoperative

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Retrospective analysis was conducted through medical records and follow-up data to evaluate preoperative scar symptoms, wound healing, and scar recurrence and improvement based on Darzi’s standard [4]. Follow-up was conducted through telephone follow-up and outpatient visits. The specific evaluation methods were as follows: general information, wound healing, preoperative scar evaluation, postoperative scar evaluation, and efficacy judgment. Efficacy judgment was based on Darzi’s scar evaluation system: “Cure” means disappearance of pain and itching symptoms, scar flat and soft, not raised above the skin, satisfactory appearance, and no recurrence within 12 months; “significant effect” means partial disappearance of pain and itching symptoms, 60 to 70% of scars are flat and soft, basic satisfaction with appearance, and no recurrence within 12 months; “ineffective” means no significant improvement in pain, itching symptoms, scar texture, and appearance, and scar area continues to develop or recur within 1 year [5]. “Cure” and “significant effect” were classified as “effective.” The effective rate was calculated as follows: Effective rate = (cure + significant effect)/total × 100%.

According to the data type, T-tests and Fisher tests were used for statistical analysis, and SPSS 25.0 statistical software was used for analysis.

Results

A total of 66 patients with 133 keloids were included in this study. Table 1 shows the specific information on gender, age, location, and etiology. The therapeutic effect was categorized as “ineffective” or “effective.” Of the 66 cases included in the study, 43 were followed up and 23 were lost to follow-up, of which 10 cases could not be reached by changing their mobile phone numbers, and the other 13 cases could not be returned for inspection because of the local closure of the COVID-19 epidemic. Of the 43 cases followed up, 4 received anti-scar treatment such as scar injection or isotope therapy within 1 year and were excluded. The remaining 39 cases were included in the study, with 16 cases (40 scar nodules) being ineffective and 23 cases (43 scar nodules) being effective. Table 2 shows the specific information on the influence of gender, age, location, etiology, start time of electron beam therapy, symptoms, and whether it was a single or multiple lesion on the therapeutic effect. (1) The effective rate for men was 67%, and for women was 54%. A chi-square test was used to analyze the relationship between gender and therapeutic effect. P = 0.517 > 0.05 indicated no statistical difference between the groups, suggesting that gender had no effect on therapeutic effect. (2) A Fisher’s exact test was used to analyze the relationship between age and therapeutic effect. P = 0.851 > 0.05 indicated no statistical difference between the groups, suggesting that age had no effect on therapeutic effect. (3) A Fisher’s exact test was used to analyze the relationship between location and therapeutic effect. P = 0.316 > 0.05 indicated no statistical difference between the groups, suggesting that location had no effect on therapeutic effect. (4) A Fisher’s exact test was used to analyze the relationship between etiology and therapeutic effect. P = 0.237 > 0.05 indicated no statistical difference between the groups, suggesting that etiology had no effect on therapeutic effect.

Table 1 Analysis of the starting time of postoperative radiotherapy with keloids
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Table 2 Factors affecting the therapeutic efficacy of keloids
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(5) A chi-square test was used to analyze the relationship between symptoms and therapeutic effect. P values were all less than 0.05, indicating that the presence of infection, pain, or itching in scar nodules before surgery had no effect on therapeutic effect. (6) A chi-square test was used to analyze the relationship between single/multiple keloids and therapeutic effect. P = 0.209 > 0.05 indicated no statistical difference between the groups, suggesting that the number of scar nodules had no effect on the therapeutic effect. (7) A Fisher’s exact test was used to analyze the relationship between the start time of electron beam therapy and therapeutic effect. P = 0.002 < 0.05 indicated a statistical difference between the groups. The start time of electron beam therapy was divided into two groups: 0–2 days and 3–5 days after surgery for comparison. A chi-square test was used to analyze the relationship between the two groups of start time of electron beam therapy and therapeutic effect. P = 0.025 < 0.05 indicated a statistical difference between the two groups. The effective rate of scar nodules that started electron beam therapy within 0–2 days after surgery was 58%, while the effective rate of scar nodules that started electron beam therapy within 3–5 days after surgery was only 25%. Figures 2, 3, and 4 show some typical cases of keloid excision combined with electron beam irradiation in our clinical practice.

Fig. 2
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Typical case 1: A 31-year-old female patient with a gradually increasing scar on her chest for 8 years with itching and pain. Scar excision was performed under general anesthesia, and electronic radiation therapy was performed on the first day after surgery. Follow-up after 12 months showed the scar was soft and painless. A Preoperative, B 12-month follow-up after surgery

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Fig. 3
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Typical case 2: A 25-year-old female patient with a progressively enlarging scar on her chest for more than 10 years. The scar was excised under local anesthesia, and the patient received electron beam therapy on the first day after surgery. At the 12-month follow-up after surgery, the scar was soft and painless. A Preoperative, B 12-month follow-up after surgery

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Fig. 4
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Typical case 3: A 28-year-old male patient with multiple scars on his body for more than 10 years. Multiple scar nodules were excised by surgery, and electronic beam therapy was performed on the day after surgery. Follow-up at 15 months after surgery showed that the scars were flat, mostly soft, painless, and itchy. A, B, C Preoperative image; D, E, F follow-up at 15 months postoperatively

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Discussion

Keloids may be related to various factors such as race, gender, age, location, and genetics. Studies have shown that people of color have a higher incidence of keloids than Caucasians, and Black people have a higher incidence than White people [6, 7]. Studies have also shown that there is no significant difference in the incidence of keloids between men and women [8, 9], but more women seek medical treatment than men, which may be related to the fact that estrogen may worsen wound inflammation [10]. During pregnancy, keloids grow rapidly, and symptoms improve after delivery [11]. In our study, one female patient had a recurrence of keloids during pregnancy. Moreover, women may have higher esthetic expectations than men. In China, the age group with the highest incidence of keloids is mainly between 10 and 30 years old [8], which is consistent with the results of this study. The low incidence of keloids in the elderly may be due to various factors, such as skin relaxation leading to lower wound tension and weaker immune response leading to weaker inflammation. Keloids tend to occur in specific sites, such as the chest, shoulders, ears, perineum, and chin. Our study also showed that the incidence of keloids in these sites is significantly higher than that in other sites, which may be related to the greater wound tension in these sites. Keloids have a clear genetic predisposition. Studies on Japanese and Chinese keloid patients have found that some genes located on chromosome 15 are closely related to keloids [12]. However, the severity of keloids in different individuals in the same family often varies, indicating that the expression of this gene is also influenced by environmental factors.

There are currently multiple scar evaluation systems available for grading the severity of scars. These include the Vancouver Scar Scale (VSS), Manchester Scar Scale (MSS), Visual Analog Scale (VAS), and Patient and Observer Scar Assessment Scale (POSAS). Various evaluation methods have their advantages and disadvantages [13,14,15,16,17]. This study is retrospective, and scar evaluation before surgery can only rely on medical records. Therefore, we designed a questionnaire based on the above scar evaluation systems to evaluate pre- and current scar conditions.

There is no unified treatment plan for scars, and treatment methods such as surgery, drug injection, laser therapy, radiation therapy, pressure therapy, and topical medications can be selected based on scar size, location, and patient preference. These treatments mainly reduce wound tension, relieve inflammation, and reduce collagen deposition to achieve the treatment goal. However, the effect of a single treatment method is not ideal, and multiple treatment methods are often combined in clinical practice to treat and prevent scars. Among them, surgical excision followed by electron beam therapy has relatively satisfactory results.

Scar hypertrophy is characterized by excessive proliferation of fibroblasts, excessive deposition of extracellular matrix, and disorderly arrangement of collagen fibers. The imbalance between fibroblast proliferation and apoptosis plays a key role. Radiation therapy uses the energy of radiation to interfere with fibroblast proliferation, thereby preventing and treating scar hypertrophy. However, because children are in an important stage of growth and development, and their systems are not yet fully mature, there are differences in their response and tolerance to drugs compared to adults. According to the 2018 domestic scar hypertrophy treatment guidelines [18], radiation therapy is not recommended for children under 16 years of age. Therefore, this study only included patients over 16 years of age.

The types of radiation therapy mainly include X-ray therapy, electron beam therapy, isotope therapy, and close-range radiation therapy. A recent meta-analysis showed that electron beam therapy was more effective than X-ray therapy after surgical excision [19]. Electron beam therapy emits β-rays, which can inhibit fibroblast proliferation, promote apoptosis, and inhibit extracellular matrix production in scar hypertrophy. It can also affect certain cytokines and gene expression, thereby inhibiting scar hypertrophy formation. However, the impact of various factors on efficacy is not yet fully understood, and our study focuses on the impact of various factors on efficacy.

Our research results showed that there was no statistically significant difference in the efficacy of surgical excision combined with electron therapy for scar hypertrophy based on patient gender, age, location, etiology, preoperative symptoms, or single/multiple lesions. Klumpar found that patient age and gender did not affect the efficacy of scar excision [20], and a 10-year single-center study by Maemoto showed that gender, age, and location did not have a statistically significant impact on efficacy, which is consistent with our results [19]. However, a study showed that the effective rate of single lesions was significantly higher than that of multiple lesions, while our study found no statistically significant difference in efficacy between single and multiple lesions [20]. Currently, there is no research that has found a clear relationship between preoperative symptoms such as pain or itching and the efficacy of surgical excision combined with electron therapy for scar hypertrophy. Our study also showed that the presence of pain, itching, or infection before surgery did not have a statistically significant impact on treatment efficacy. Local pain, itching, and infection are manifestations of a more severe local inflammatory response, and after surgical excision, the healing of the wound may not be related to preoperative symptoms. We analyzed the impact of the start time of postoperative electron therapy on the efficacy of scar hypertrophy treatment, and our results showed that the effective rate of electron therapy performed within 0–2 days after surgery was significantly higher than that performed after 2 days, which is consistent with the mainstream view. Most studies have shown that the effective rate of electron therapy for scar hypertrophy is higher within 24–48 h after surgery [21, 22]. Fibroblasts and immature collagen within the incision are more sensitive to electron therapy during the early stages of wound healing, and electron therapy has a stronger effect on fibroblasts during this stage [23]. There is no evidence that the treatment dose of radiation therapy will cause scar hypertrophy or malignant tumors in the surrounding healthy skin [3], and our follow-up study did not find any malignant tumors in the surrounding skin after electron therapy.

The etiology of scar hypertrophy and the factors that affect treatment efficacy are complex, and there is no clear conclusion [9, 24,25,26]. In our study, different doctors in our department and radiation oncologists may have performed the surgical operation and electron therapy plan, respectively, which may introduce differences in surgical and electron irradiation techniques that may affect the research results. Some studies have shown that scar hypertrophy volume (length × width × thickness) measured by CT scan is significantly correlated with recurrence, while length alone is not [27]. However, this study was limited by its retrospective design, and the medical records were not comprehensive enough to accurately measure scar hypertrophy, making it difficult to explore this aspect. Since most patients were discharged before suture removal, wound care after discharge may also affect wound healing, such as inadequate disinfection, failure to remove scabs in time, and vigorous activity that may worsen wound inflammation and affect treatment efficacy. These factors will be further studied in future research.

Conclusion

In this study, we performed statistical analysis on the influence of follow-up patient factors such as gender, age, location, cause, preoperative symptoms, and single/multiple occurrence on the therapeutic effect, and no statistical differences were found (P > 0.05). Statistical analysis was also performed on the relationship between the start time of electron beam therapy after surgical excision and the therapeutic effect, and the difference was statistically significant (P = 0.025). It was found that the effective rate was higher when electron beam therapy was performed 0–2 days after surgery compared to 3–5 days after surgery.