A Keloid Edge Precut, Preradiotherapy Method in Large Keloid Skin Graft Treatment WENBO LI, MD, YOUBIN WANG, MD, XIAOJUN WANG, MD, AND ZHIFEI LIU, MD* BACKGROUND Keloids are scars that extend beyond the borders of the original wound. They are difficult to cure because of their high recurrence rate, particularly in large keloids that require skin grafts. This article describes a study to compare the effectiveness of a new technique, a combination precut, preradiotherapy method, with the conventional surgical method of keloid skin graft treatment. METHODS Fifty-three patients with chest wall keloids were treated from April 2005 to June 2011. Twentynine patients were treated with conventional surgery and radiotherapy. Keloids were removed from these patients, and their wounds were closed with skin grafts. If the grafts survived well, radiotherapy was applied, and the sutures were removed. Twenty-four patients were treated using the novel precut, preradiotherapy method. An incision was made down to the subcutaneous layer around the edge of the keloid, and radiotherapy was applied on the following day. Then the keloid was removed, and the wound was closed using a skin graft. Radiotherapy was applied for the second time when the graft was found to have survived. Patients underwent follow-up examinations 6 and 12 months after surgery. The scar at the operation site and aesthetic satisfaction were recorded and compared. RESULTS The recurrence rate was 55.2% in the conventional group and 16.7% in the precut group, a significant difference (v 2 = 6.73, p <.01). There was a significant difference in aesthetic satisfaction between the two groups, with 48.3% in the conventional group rating their satisfaction as poor versus 8.3% in the precut group (v 2 = 7.50, p <.01). CONCLUSION The precut, preradiotherapy strategy may be a promising treatment option for patients with large keloids that require excision and skin graft repair. Wenbo Li and Youbin Wang contributed equally to this article. A keloid is a benign growth caused by an overabundance of collagen deposits. Surgical excision is one of the major methods used for keloid treatment. In patients with large keloids, the wound is sometimes difficult to close after the keloid has been removed, and skin grafts and skin flap transplantations are often necessary, 1,2 but skin flaps are not available in all patients. Skin grafts are the only remaining option for covering defects in some patients. Surgical excision without other adjuvant treatment is less effective in keloid treatment. The recurrence rate is reportedly between 45% and 100% in cases treated with surgical excision alone. 3 Combining surgical excision with adjuvant radiotherapy can provide satisfactory results without recurrence in up to 97% of cases. 4 Radiotherapy is most effective when it is applied immediately, ideally on the day of the surgical excision and no more than 24 48 hours after surgery, 3 but in patients receiving skin grafts, the application of radiotherapy treatment within these time constraints is not practical because of surgical bandage impedance and concerns about graft survival. Therefore, radiotherapy treatment is often postponed to 14 days after surgery (when the graft has survived). We designed the keloid edge precut, preradiotherapy method to address the problems of delayed radiotherapy. *All authors are affiliated with Department of Plastic Surgery, Peking Union Medical College Hospital, Peking, China 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:52 57 DOI: 10.1111/dsu.12374 52
LI ETAL Patients and Methods Patient Group Fifty-three patients with chest wall keloids were treated in our center from April 2005 to June 2011. Mean keloid size was approximately 5.4 by 9.8 cm. The wounds in these patients could not be directly closed after keloid excision, and skin grafts were required. The patients were randomly divided into two groups based on the month during which the operation was performed. Patients whose operations were performed in January, March, May, July, September, and November were placed in the conventional method group. Patients whose operations were performed in alternating months were placed in the precut, preradiotherapy group. There were 29 patients (19 male, 10 female, mean age 23 5) in the conventional group. Mean keloid size was 5.6 by 9.3 cm. They were treated using conventional surgery and radiotherapy. There were 24 patients (13 male, 11 female, mean age 21 6) in the precut, preradiotherapy group. Mean keloid size was 5.2 by 10.3 cm. They were treated using our novel precut, preradiotherapy method. All patients with chest wall keloids in this study had no history of smoking or autoimmune disease. There was no significant difference in mean size of keloid and wound between the two groups. Patients received follow-up examinations from two experienced nurses in our center 6 and 12 months after surgery. The Institutional Review Board of Peking Union Medical College Hospital approved the experimental protocols, and all patients had previously provided informed consent. Surgical and Radiotherapy Methods Conventional Surgical and Radiotherapy After intravenous general anesthesia was administered, the edge of the keloid was marked. The keloid mass and normal skin vicinity was infused with 0.5% lidocaine (1:100,000 epinephrine). The keloid mass was then excised along the mark. The size of the wound was measured, and an intermediate splitthickness skin graft was harvested from the groin. After step-by-step bipolar coagulation, the wound was covered with the skin graft and a bolus pressure dressing. The dressing was removed between postoperative days 10 and 14. Radiotherapy was used for the first time after the dressing was removed and again 7 days later (900 cgy each time). Radiotherapy was applied at the groin on days 1 and 7 after the graft harvest operation (900 cgy each time). Precut, Preradiotherapy Method Anesthesia was administered, and a mark method similar to that of the conventional method was used. After the keloid edge and normal peripheral skin were infused with 0.5% lidocaine (1:100,000 epinephrine), an incision was made along the mark deep into the subcutaneous fat. After bipolar coagulation, the incision was approximated using a continuous intradermal suture. The surgical site was covered with surgical dressing, and radiotherapy was performed within 24 hours (900 cgy). The patient received a second operation the following day. After administration of anesthesia, the sutures were removed, and the keloid mass was excised. The size of the wound was measured, and an intermediate split-thickness skin graft was harvested from the groin. After hemostasis, the wound was covered with the skin graft and a bolus pressure dressing. The dressing was removed between postoperative days 10 and 14, and the second round of radiotherapy was performed (900 cgy). Radiotherapy at the groin was performed as for the conventional method. Evaluation after Therapy Two experienced nurses in our center evaluated the scar at the surgical site during the follow-up period. They were experienced in scar evaluation but had no awareness of the detailed treatment for each patient. They took photographs of each patient at follow-up and completed the evaluation at the same time. The scar was rated using the following guidelines: 40:1:JANUARY 2014 53
KELOID EDGE PRECUT PRERADIOTHERAPY METHOD Ordinary scar: flat, pale in color, within the limits of the operation incision; the patient may experience an occasional tingling sensation at the site of the scar. Hypertrophic scar: protuberant, red or purplish-red in color, within the range of the operation incision; the patient often experiences itching and aching. Keloid scar: protuberant, red or purplish-red in color, exceeds the range of the operation incision; the patient often experiences significant itching and aching. The evaluator nurses graded the keloid therapy results at follow-up as follows: cured, an ordinary scar at the surgical site; partially cured, a hypertrophic scar in a part or the entirety of surgical site; recurrence, a keloid scar in a part or the entirety of the surgical site. Patients aesthetic satisfaction was also recorded and evaluated at the final visit. The questionnaires were used to gather information about the opinions of patients. The aesthetic results were graded as good, acceptable, or poor. No detailed guidelines were given to the patients when conducting these satisfaction questionnaires. The recurrence and aesthetic satisfaction rates were recorded and compared. Data were analyzed using SPSS 17.0 software (SPSS, Inc., Chicago, IL). Recurrence and satisfaction rates of the two groups were compared using the chi-square test. Results Twenty-nine patients were treated with conventional surgery and radiotherapy. In these patients, 16 cases of keloid recurrence were observed (Table 1); the recurrence rate was 55.2%, and the cure rate (including cured and partially cured scars) was 44.8%. Recurrent keloids extended along the surgical incisions, expanding beyond the incision range. The keloid mass was hard and red or purplish- red in color. The grafted skin was contracted, crimped, and TABLE 1. Keloid Treatment Results According to Treatment Method Cured Partially Cured Recurred Treatment Method n (%) n (%) n (%) Conventional, 2 (6.9) 11 (37.9) 16 (55.2) n = 29 Precut, n = 24 11 (45.8) 9 (37.5) 4 (16.7) dark in color (Figures 1 and 2). Fourteen (48.3%) of the patients in this group were dissatisfied with the aesthetic results (poor grade), 20.7% thought that the aesthetic results were good, and 31.0% thought the results were acceptable (Table 2). Twenty-four patients were treated using the precut, preradiotherapy method. Four of these (16.7%) experienced keloid recurrence in the follow-up period. The cure rate (including cured and partially cured scars) was 83.3%. The recurrence rate in this group was significantly lower than that in the conventional method group (v 2 = 6.73, p <.01) (Table 1). The incision scar was flat, soft, and pale. The grafted skin was also flat and pale. There was no obvious graft contraction (Figures 3 and 4), and only two (8.3%) of the patients in this group were dissatisfied with the aesthetic results (poor). The majority of patients rated the aesthetic results as good (50.0%) or acceptable (41.7%) (Table 2). There was also significant difference in the aesthetic results between the two groups (v 2 = 7.50, p <.01). Discussion Keloid formation and expansion is related to skin tension. Keloids often occur in the anterior chest, shoulder, scapular, and suprapubic regions, 5 sites that are constantly subjected to mechanical forces from body movement. Ogawa thought that mechanical forces may not only promote keloid growth, but also be the primary trigger of their generation. 6 Therefore, reducing the mechanical force on healing skin would help to prevent the development and recurrence of keloids. 7 54 DERMATOLOGIC SURGERY
LI ETAL Figure 1. Case 1 in the conventional surgical and radiotherapy method group. Figure 2. Case 2 in the conventional surgical and radiotherapy method group. Many methods have been used to reduce the mechanical force on wounds. In cases of small keloids, the wound edge after keloid removal can be TABLE 2. Aesthetic Results According to Treatment Method Treatment Method Conventional, n = 29 Good Acceptable Poor n (%) n (%) n (%) 6 (20.7) 9 (31.0) 14 (48.3) Precut, n = 24 12 (50.0) 10 (41.7) 2 (8.3) closed directly. Tensile reduction sutures are often used to reduce wound tension. 6 In patients with larger keloids, the wound often cannot be closed directly, and a skin flap must be used to distribute the wound tension, 7 but a skin flap is not always available. In patients with large keloids, a local skin flap cannot provide sufficient skin coverage. Furthermore, some patients refuse to accept a skin flap procedure because it requires additional incisions at the same surgical site. In these cases, skin Figure 3. Case 1 in the precut, preradiotherapy method group. Figure 4. Case 2 in the precut, preradiotherapy method group. 40:1:JANUARY 2014 55
KELOID EDGE PRECUT PRERADIOTHERAPY METHOD grafts might be performed; 2 tissue expansion can also be used in some cases. 8 Surgical therapy can be used to remove the keloid mass and resurface the wound, but surgical excision without any postsurgical treatment is not sufficient to prevent keloid recurrence. The reported recurrence rate is between 45% and 100% in patients treated with surgical therapy alone. 3 Many types of adjunctive therapies after keloid operations have been reported, including radiation therapy, 3 steroid injection, 9 imiquimod therapy, 10 and pressure. 11 Radiation therapy is the most effective of these methods. 3 The recommended radiation therapy procedure is to radiate the surgical site within 24 or 48 hours after the operation. 3 The recommended radiation doses (single or cumulative) and intervals between applications vary. 3 It has been reported that radiotherapy with a single 900-cGy dose is effective when applied on postoperative day 1 or 7. 12 Radiotherapy can easily be applied if the wound is directly closed using a tensile reduction suture, skin flap transference, or tissue expansion, but radiotherapy cannot be applied within 24 or 48 hours after surgery if the wound is closed using a skin graft. The bolus dressing and bandage will impede radiotherapy. Radiation injury at this time will also negatively influence graft survival. Radiotherapy is often postponed until the suture is removed and the graft is determined to have survived. The effects of radiation on keloids are thought to be mediated through the inhibition of neovascular buds and proliferating fibroblasts, which results in less collagen production. 13 Failure to apply early-stage radiotherapy leads to more neovascular formation and fibroblast proliferation and increases the recurrence risk. To solve the problem of the inconvenience of early-stage radiotherapy in patients with keloids treated with skin grafts, we rearranged the order of the procedure. First, we precut the edge of the keloid. The incision was made in the normal skin near the keloid, deep into the subcutaneous layer. The incision was then approximated with continuous intradermal sutures after bipolar coagulation. To prevent wound infection, the keloid was not removed at that time. The tissue trauma and systemic reaction that this procedure caused were almost the same as those that conventional keloid removal surgery causes. Radiotherapy was applied approximately 24 hours after surgery. This treatment procedure greatly suppressed neovascular formation and fibroblast proliferation reaction around the incision. The third step involved keloid removal and skin graft procedures. This step was performed on the day after radiotherapy. The skin graft was typically harvested from the groin, and the groin wound was closed directly. The second radiotherapy treatment was the final step in the treatment procedure. This procedure was usually performed between postoperative days 10 and 14, at which time the sutures were removed, and graft survival was evaluated. With the precut method, the sequence of the conventional treatment procedure was rearranged to enable early-stage radiotherapy. Our clinical data demonstrated the good surgical and aesthetic results of the treatment. The precut method achieved a lower keloid recurrence rate than the conventional method. The aesthetic satisfaction rate in the precut group was also higher than that in the conventional group. The clinical data have demonstrated the effectiveness of early-stage radiotherapy, but the mechanism of this effect remains unclear. Radiotherapy may suppress the inflammatory reaction as well as neovascular formation and fibroblast proliferation to promote healing after keloid scar removal. Conclusion Early-stage radiotherapy is an important adjunctive therapy for the prevention of postoperative keloid recurrence. In patients treated with skin grafts, early-stage radiotherapy is often hindered. With the precut, preradiotherapy method, the conventional treatment procedure was rearranged to permit 56 DERMATOLOGIC SURGERY
LI ETAL early-stage radiotherapy. A low recurrence rate and satisfactory clinical results were achieved with this method. Precut, preradiotherapy treatment may be a promising choice for patients with large keloids that require skin graft operations. References 1. Hatoko M, Kuwahara M, Shiba A, Tada H, et al. Earlobe reconstruction using a subcutaneous island pedicle flap after resection of earlobe keloid. Dermatol Surg 1998;24:257 61. 2. Brown NA, Ortega FR. The role of full-thickness skin grafting and steroid injection in the treatment of auricular keloids. Ann Plast Surg 2010;64:637 8. 3. Froelich K, Staudenmaier R, Kleinsasser N, Hagen R. Therapy of auricular keloids: review of different treatment modalities and proposal for a therapeutic algorithm. Eur Arch Otorhinolaryngol 2007;264(12):1497 508. 4. Ragoowansi R, Cornes PG, Moss AL, Glees JP. Treatment of keloids by surgical excision and immediate postoperative singlefraction radiotherapy. Plast Reconstr Surg 2003;111:1853 9. 5. Ohmori Y, Akaishi S, Ogawa R, Hyakusoku H. Analysis if regions where keloids tend to occur. Scar Management. 2010;4:112 5. 6. Ogama R, Akaishi S, Chenyu H, Dohi T, et al. Clinical applications of basic research that shows reducing skin tension could prevent and treat abnormal scarring: the importance of fascial/subcutaneous tensile reduction sutures and flap surgery for keloid and hypertrophic scar reconstruction. J Nippon Med Sch. 2011;78(2):68 76. 7. Aoki M, Akaishi S, Ono S, Iwakiri I, et al. Usefulness and problems of flap surgery for keloids. Scar Management 2010;4:108 11. 8. Roeder JA, White SK. Tissue expansion for the treatment of keloids. Plast Surg Nurs. 1990;10(3):114 7. 9. Mustoe TA, Cooter RD, Gold MH, Hobbs FD, et al. International clinical recommendations on scar management. Plast Reconstr Surg 2002;110:560 71. 10. Stashower ME. Successful treatment of earlobe keloids with imiquimod after tangential shave excision. Dermatol Surg 2006;32:380 6. 11. Kelly AP. Medical and surgical therapies for keloids. Dermatol Ther 2004;17:212 8. 12. Zheng Q, Weizhong L, Youbin W, Xiao L, et al. X shaped incision and local skin flap: a new surgical method for auricle keloid excision and reconstruction. Dermatol Surg 2012;38:1378 82. 13. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, et al. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med 2011;17(1 2): 113 25. Address correspondence and reprint requests to: Youbin Wang, MD, Peking Union Medical College Hospital, Beijing 100032, China, or e-mail: wy.benz@aliyun.com 40:1:JANUARY 2014 57