Efficacy and safety of surgical excision and reconstruction combined with radiotherapy for huge keloids: A 13‐year experience

Surgical excision combined with radiotherapy is considered an effective treatment for keloids, while the efficacy and safety of this regimen for huge keloids in patients who need reconstruction after excision is still unclear. Therefore, this study aimed to evaluate the efficacy and safety of surgical excision and reconstruction combined with radiotherapy for huge keloids in a single center with 13 years of experience.


| INTRODUC TI ON
Keloids are pathological fibroblast proliferation scars resulting from trauma or surgical incisions. 110] In many cases, closure can be achieved with simple sutures after the excision of small and single keloids, while wounds in patients with huge keloids cannot be closed with low-tension primary sutures.[13][14] However, outcomes for patients with huge keloids who underwent excision and reconstruction combined with radiotherapy were still unclear, especially the impact of radiotherapy on reconstructive methods.Therefore, the present study aimed to evaluate the efficacy and safety of surgical excision and reconstruction combined with radiotherapy for huge keloids in a single center with 13 years of experience.

| Study design
This study was approved by the Institutional Review Board with a waiver of informed consent.We reviewed consecutive patients with keloids between January 1, 2009, and December 31, 2021.Inclusion criteria were all as follows: (1) surgical excision of keloids followed by reconstruction with z-plasties, skin grafts, or skin flaps; (2) follow-up for at least 12 months.Exclusion criteria were any of the following: (1) patients received other postoperative adjuvant treatments, such as laser, cryotherapy, injection of corticosteroid, 5-Fluorouracil, or botulinum toxin, and so on; (2) surgical excision of keloids with simple sutures; and (3) patients without complete medical records.Clinical data were reviewed for demographic information, prior interventions for the keloids, surgical/radiotherapy parameters, surgical/radiotherapy complications, and recurrence rates.Surgical parameters included locations and sizes of keloids, reconstructive methods, and skin grafts/flaps sizes.

| Keloids excision
After intravenous general anesthesia, the margins of the keloid were marked.The keloid and adjacent normal skin were infused with 0.5% lidocaine (1:100000 epinephrine).The keloid was then excised along the markings and sent for histopathological examination to confirm the diagnosis.Core or partial excision was recommended when total excision of a huge keloid was technically unfeasible or would cause significant deformity.

| Z-plasties
One or more z-plasties should be utilized to disperse the tension when the incision line used to remove the keloid follows the main direction of skin tension.A central vertical incision was created in line with the long axis of the wound; then, two triangular flaps of the same size and angle were transposed to fill the defect with each other.A 60° z-plasty with a 1 cm or less triangular flap was recommended.

| Skin grafts
The size of the wound was first measured to determine the size of the skin graft.Donor site for full-thickness skin grafts was designated in an elliptical shape and easily harvested with a scalpel.Perforating the skin graft would increase the potential area coverage and survival.Sheet skin grafts would be desirable in aesthetically vulnerable locations.With a mechanical dermatome, split-thickness skin grafts can be harvested rapidly.A bolster pressure dressing or negative pressure wound therapy device was applied to prevent separation of the graft from the wound due to shear forces or subgraft fluid accumulations.The dressing or NTWP was removed between the 10th and 14th postoperative day.

| Skin flaps
A skin flap was designed slightly larger than the wound with a sufficient rotational arc after keloid excision.The flap was completely detached by electrocautery and elevated from distal to proximal all the way to the perforator, and then inserted into the defect.The donor defect was closed primarily with minimal subcutaneous undermining.Sometimes, skin grafting was required at the donor site for larger flaps.

| Postoperative radiotherapy
An external beam with 6 MeV electrons was administered within 24 h postoperatively to patients with z-plasties or skin flaps.A total dose of 18 Gy in 3 fractions (6 Gy each session) 1 day apart was prescribed.For patients with skin grafts, the first radiotherapy was performed after removal of the dressing and again 7 days later (9 Gy each session).
The radiation field should include the entire scar (including structure/puncture hole) with a 2 cm of margin around the lesion.Use 0.5 cm of wax to improve the surface dose and 0.8 cm of customized lead sheet to shield non-target areas.

| Postoperative management
Postoperative management mainly consisted of suction drains, wound dressings, and prophylactic antibiotics in need.Patients were followed up routinely every 3-6 postoperative months via outpatient clinic or by telephone until 1 year and then on-demand.
Reconstructed defects and donor sites were evaluated for keloids recurrence.

| Case 1
An 18-year-old man presented with an anterior chest wall keloid due to acne (Figure 1).The keloid (5 cm × 6 cm) was completely excised and reconstructed with z-plasties, then followed with radiotherapy (18 Gy in 3 fractions over 3 days) within 24 h postoperatively.The postoperative course was uneventful.

| Case 2
A 61-year-old woman developed an anterior chest wall keloid without known risk factors (Figure 2).The patient previously received corticosteroid injections twice, and the results were unsatisfying.The keloid (15 × 2 cm) was excised partially and reconstructed with a scalp graft.The first time radiotherapy was performed after the removal of dressing and again 7 days later (9 Gy each session).No surgical/radiotherapy complications or recurrence was observed during an 84-month follow-up.

| Case 3
A 40-year-old woman had keloid due to cesarean delivery (Figure 3).
The keloid (7 × 5 cm) was completely excised and reconstructed with a groin flap (15 × 6 cm), then followed with radiotherapy (18 Gy in 3 fractions over 3 days) within 24 h.No surgical/radiotherapy complications or recurrence was observed during a 20-month follow-up.

| DISCUSS ION
The results of the present study showed that surgical excision and reconstruction combined with scheme of 18 Gy (Biologically Effective Doses, BEDs, approximately 30 Gy) might be safe and effect for patients with huge keloids.Keloids can be efficiently treated or prevented with radiotherapy with suppressed angiogenesis and inflammation.As BEDs increased, so did the control rate, whereas when BEDs exceeded 30 Gy, it approached a plateau with no additional clinical efficacy but greater side effects. 9,10plasties will disperse the tension over the length of the wound and help reduce the recurrence of keloid. 11A systematic review and meta-analysis evaluated outcomes after surgical resection and radiotherapy on 400 patients with chest keloids and identified the recurrence rate was 22%. 15Adding z-plasties to this protocol reduced the recurrence rates to 10.6% in anterior chest wall keloids (n = 141) and 5.3% in upper-arm keloids (n = 38) during a 24-month follow-up. 12,13ly temporary pigmentation and telangiectasia were observed, without wound dehiscence or other severe complications.Similarly, patients in our z-plasties group achieved recurrence rate of 14.3% (2/14) and only two patients suffered temporary hyperpigmentation.
Skin grafts have been demonstrated as an effective reconstructive method for moderated and large keloids.Brown and Ortega 16 retrospectively analyzed total excision followed by full-thickness skin grafting and steroid injection in the treatment of auricular keloids in 10 children, and no recurrence was found during an 11-month follow-up.Rasheed and Malachy 14 used split-thickness skin graft and steroid injection after intralesional excision of six moderate and large helical rim keloids and achieved satisfactory aesthetic results in all patients.It is worth noticing that radiotherapy within no more than 24-48 h after skin grafting may be impractical due to impedance of surgical dressing and concerns about graft viability.However, previous studies did not find serious side effects of radiotherapy on skin TA B L E 1 Demographic, surgical, and recurrence variables of patients with z-plasties.grafts. 17,18In addition, delayed radiotherapy may increase the recurrence rate of keloids, so the researchers tried different approaches to start radiotherapy as early as possible.Li et al. 19 found that precut, pre-radiotherapy method (n = 24) resulted in a recurrence rate of 16.7%, compared with conventional skin grafts with delayed radiotherapy (n = 29) of 55.2%.The duration of the interval was less than 24 h in the pre-radiotherapy group and 10-14 days in the conventional group.Therefore, in conditions of skin graft survival, radiotherapy should be administered immediately after the removal of the dressing (1 week after surgery, if possible).
Skin flaps are strongly vascular and less susceptible to vascular damage caused by radiotherapy.Japan Scar Workshop Consensus Document (2018) 11 recommended that radiotherapy should be administered to skin flaps no more than 24 h after keloids excision, except for blood flow defects.A meta-analysis reported no significant differences in complication rates when comparing immediate autologous breast reconstruction with and without postoperative radiotherapy. 20However, few studies, espe- Number and proportion were used to summarize categorical variables, and mean and standard deviation were used to summarize continuous variables.All statistical analyses were performed with SPSS statistical software (version 26.0, SPSS, IL, USA).
in the skin flaps group.Nearly half (9/21) of the keloids in this study were recurrent.Prior treatments were surgical excision, corticosteroid injection, radiotherapy, or a combination.Histopathological examinations of keloids were not identical in all patients, one patient was diagnosed with dermatofibrosarcoma protuberans, one with spindle cell lipoma, and one with an epidermoid cyst.All patients with z-plasties or skin flaps underwent radiotherapy within 24 h postoperatively, and two patients in z-plasties group developed temporary hyperpigmentation, without other radiotherapy complications.One patient, who underwent reconstruction with a skin flap, developed local necrosis and healed after conservative treatment without the need for surgical revision.All patients reported relief of severe pain and itch, except for two patients (2/14) in the z-plasties group suffered partial keloids recurrence and were healed with corticosteroid injection.The overall appearance of reconstructed defects was aesthetically acceptable.No wound infection, telangiectasia, or new keloids at donor sites were observed during the mean follow-up time of 75 months (ranging from 12 months to 13½ years).

F I G U R E 1 F I G U R E 3
cially prospective randomized controlled trials with large sample sizes, have ever evaluated the irradiation complications on skin flaps after keloid excision.Ogawa et al. 21retrospectively analyzed internal mammary artery perforator pedicled propeller flaps combined with postoperative high-dose-rate superficial brachytherapy for 10 patients with huge anterior chest wall keloids, and no surgical complications or recurrence was observed during a mean follow-up of 28.7 months.Treatment of an anterior chest wall acne keloid by using z-plasty and postoperative radiotherapy.(Above, left) Preoperative view.(Above, right) Design of z-plasty.(Below, left) Immediately after surgery.(Below, right) Three months after surgery.F I G U R E 2 Treatment of anterior chest wall keloid by using scalp graft and postoperative radiotherapy.(Above, left) Preoperative view.(Above, right) Immediately after partial keloid excision.(Below, left) Immediately after scalp grafting.(Below, right) Twelve months after surgery.Treatment of abdomen keloid with a groin flap and postoperative radiotherapy.(Above, left) Preoperative view and design of a groin flap.(Above, right) Immediately after total keloid excision.(Below, left) Immediately after surgery.(Below, right) One month after surgery.