Management of radiation-induced ulcers by singlestage reconstructive surgery: a prospective study

Summary

Radiation-induced ulcers are a late-stage skin reaction after radiation therapy for cancer treatment. The present study examined the possibility of using a single-stage reconstructive procedure to manage radiation-related wounds. This prospective study recruited 30 participants who underwent radiation treatment for cancer or hemangioma. The patients ranged in age from 15 to 80 years. They were admitted to the Plastic, Reconstructive, and Regenerative Centre of Viet Nam National Burn Hospital from October 2013 to September 2017. For each patient, the surgeons discussed which reconstructive method would yield the best outcome. Patients’ demographic data and information on the radiation-induced ulcer, the reconstructive method used, complications, and length of hospital stay were recorded. The mean age of all participants was 50 ± 36.3 years, and female patients were predominant (83.3%). Eighteen perforator flaps, five random-pattern flaps, three free flaps, three tissue expander flaps, and one full-thickness skin graft were employed, with no instances of recurrence or complications, except for total flap loss in two cases. The median length of stay was 43 days. These data suggest that immediate reconstruction may be a valuable option for managing radiation-induced ulcers.

Introduction

In recent decades, although radiotherapy (RT) has shown tremendous benefits for cancer treatment, its side effects have been reported in many studies. Radiation-induced ulcers are a late-stage skin reaction after RT, with a considerable direct impact on patients’ life.¹ In a previous report, a moderate-to-severe skin reaction was seen in 85% of patients who underwent RT.¹ It has been clearly documented that radiation-induced ulcers cannot heal by themselves due to the reduced blood supply in the surrounding tissue, fibrosis and impaired cellular repair potential.^2,3 Subsequently, radiation-induced ulcers often become infected, reducing the viability of the granulation tissue.⁴ Therefore, the management of radiation-induced ulcers to reduce the complications of RT has emerged as a clinically important issue.

As described in the literature, chronic radiation-induced ulcers can be treated with advanced treatments such as mesenchymal stem cells, hyperbaric oxygen therapy, superoxide dismutase, and low-intensity laser therapy.⁵ However, some of these modalities need more study, and one study has reported that hyperbaric oxygen therapy and conventional wound care had few benefits.⁶ That study also described the use of excision and reconstructive methods such as local flaps, rotation flaps and split-thickness skin grafts in a single-stage procedure to manage the ulcer. Another study compared single and two-stage reconstruction for radiation-induced ulcers in the chest wall.⁷ However they did not recommend any particular reconstructive technique, except the omentum majus flap and skin grafting. In this paper, we examine the use of immediate reconstructive methods to treat radiation-induced ulcers in patients with a history of RT.

Materials and methods

We designed this study as a prospective investigation. It was conducted at the Plastic, Reconstructive and Regenerative Centre of the Viet Nam National Burn Hospital, which is the largest burn centre in northern Vietnam, from October 2013 to September 2017. This study recruited 30 patients who underwent RT because of cancer or hemangioma. The patients’ age ranged from 15 to 80 years. They did not have any contraindications for general surgery. The exclusion criteria were: (1) patients still receiving cancer treatment, (2) patients with mental health problems, and (3) patients with severe diseases, such as heart, kidney or liver failure.

From patients’ medical records, data were collected on demographic features, characteristics of the ulcers (time of appearance after RT, position and wound dimensions, including those of the ulcer, affected area, resected area and flap), detailed information about the procedures (including the type of flap), and postoperative outcomes (flap status, complications, recurrence and length of stay [LOS]).

After providing written informed consent, all participants underwent a careful clinical examination, with a particular focus on the radiation-induced ulcer. We divided the ulcers into three categories (first-degree, second-degree and third-degree), as follows: first-degree ulcers presented with atrophy, scleroderma, dark pigmentation (multiple pigmentations) and hair loss; second-degree ulcers were small (diameter <7.5 cm) and non-invasive to the muscle layer; and third-degree ulcers were non-healing (diameter ≥7.5 cm) and invasive to the muscle layer or deeper (Fig.1).⁸ In addition, discussions were held among the plastic surgeons to determine which procedure would yield the best result for each patient. Five surgical methods were used in this study: (1) full-thickness skin grafts (FTSG), (2) tissue expanders, (3) randompattern flaps, (4) perforator flaps or axial-pattern flaps, and (5) free flaps. The dimensions of each flap were designed intraoperatively based on the excised area. The donor site was healed by wound closure or an autologous skin graft.

Fig. 1a. The classification of radiation-induced ulcers by Le The Trung 2001⁸. A first-degree ulcer.

Fig. 1b. A second-degree ulcer.

Fig. 1c. A third-degree ulcer.

The primary outcomes in this study were flap status and LOS. For all characteristics except age, the median and percentage were calculated because they did not follow a normal distribution. All data were analyzed using R version 3.6.

Results

Thirty patients who were admitted to the Viet Nam National Burn Hospital from October 2013 to September 2017 met the inclusion and exclusion criteria. Twenty-five (80%) of the patients were female. The mean age of all participants was 50 ± 36.3 years, while that of patients with breast cancer history was 60 ± 12 years. Only two patients had a history of diabetes mellitus. Breast cancer was the most common indication for RT (40%), followed by hemangioma and other reasons. Similarly, the chest was the most common location of ulcers. The median interval between RT and ulcer development was 7.5 years (range, 1–31 years). The median LOS in the hospital was 43 days, and no short-term complications occurred (Table I).

Table I. Characteristics of 30 radiation-induced ulcer patients who were treated at the Viet Nam National Burn Hospital from October 2013 to September 2017.

Intraoperative data and postoperative outcomes are presented in Table II. During the operation, the dimensions of the ulcers and flaps were measured, and after surgery the status of the flaps was assessed. The average area of the ulcers was 3 × 5 cm2, while the dimensions of the affected and resected sites were 10 × 10 cm2 and 10 × 8 cm2, respectively. Pedicle flap was both the largest (average dimensions, 15 × 9 cm²) and by far the most commonly used procedure (60% of cases), followed by random-pattern flaps, expanders, free flaps and FTSG. Two perforator flaps experienced partial necrosis, and two others developed total necrosis, including one deep inferior epigastric perforator (DIEP) free flap for breast reconstruction, which led to another operation for total healing of the wound. Moreover, 9 latissimus dorsi myocutaneous flaps (LDMFs) at the first operation and another at the second operation were used for chest ulcers (i.e., in patients with breast cancer), with a flap survival rate of up to 90% (Fig. 2). Two expander flaps were applied to deal with the consequence of radiation therapy in hemangioma (Fig.3). One case with tongue cancer history presented with 1^st-degree on the side of his neck so the horizontal scapular flap was designed (Fig.4). Three Superior Gluteal Artery Perforator Flaps illustrated their advantages in managing the ulcer on the buttock region. (Fig. 5) shows a patient suffering from cervical cancer radiation treatment. The DIEP free flap illustrated its advantages in breast reconstruction with high aesthetic outcome (Fig.6). In 6 months of follow-up, none of the 30 patients experienced recurrence.

Table II. Intraoperative data and postoperative results for 30 radiation-induced ulcer patients.

Fig. 2. Radical excision and immediate reconstruction with a perforator flap. (Above, left) 44-year-old woman with a history of radiotherapy for breast cancer presented with a radiation-induced ulcer; (above, centre) partial excision of the necrotic and affected areas; (above, right) design of a latissimus dorsi myocutaneous flap (LDMF); (second row, left) flap elevation during operation; (second row, right) immediate reconstruction with the LDMF; (below, left and centre) the wound had healed smoothly at 3 months after surgery with no recurrence; (below, right) donor site after 3 months.

Fig. 3. A radiation-induced ulcer was treated using a tissue expander. (Left) A 36-year-old woman underwent radiotherapy to treat a hemangioma; (centre) photograph of the patient after removal of the expander and reconstruction; (right) a good result was observed 6 months later.

Fig. 4. A free flap was applied after excision of a radiation-induced ulcer. These four pictures illustrate the process of treatment of a radiation-induced ulcer in this 44-year-old male patient. (Above) Before and after the operation; (below, left) one day after the operation; (below right) favorable results of the procedure at 7 days after the operation.

Fig. 5. A typical superior gluteal artery perforator flap was designed to cover the buttock region. (Above, left) A 60-year-old woman with a history of cervical cancer and a radiation-induced ulcer; (above, right) design of the flap; (below, left) the result after surgery; (below, right) the outcome at 3 months postoperatively.

Fig. 6. Three above pictures show the designed DIEP free flap in breast reconstruction. (Left) Indicated the affected area in the right breast and design flap in the donor side; (centre) elevated flap; (right) the result after operation.

Discussion

It is well established that reconstructive procedures play an important role in the management of radiation-induced ulcers because conservative therapy for such ulcers is not effective. We found that single-stage reconstruction was highly suitable for RT-related wounds and that a variety of flap types can be applied upon the ulcerated areas.

Our study focused on single-stage procedure as a way to achieve good outcomes but did not yield a direct recommendation regarding whether immediate reconstruction is preferable to two-stage reconstruction, unlike a previous study.⁷ Based on the LOS and the likelihood of ensuring lower hospitalization fees and a lower likelihood of repeated operations, we chose to perform wide debridement and reconstruction in a single procedure for all patients.

Breast reconstruction is an important aspect of managing chest ulcers after radiation for breast cancer. The DIEP free flap has been used for more than 20 years to reshape the breast, and the LDMF for more than 50 years. The DIEP free flap is widely used as the first choice at many centres throughout the world because of its advantages, but its suitability depends on several factors, including the experience of the surgeon, the available technical equipment, and the characteristics of the patient.^9,10,11

Of particular importance, patients with excess fat in the lower abdomen may not be suitable for an intensive operation with a long anaesthetic induction. In contrast, the LDMF is preferable to the DIEP flap because it only requires a short duration of sedation. In addition, breast volume is usually smaller in Asian patients than in Caucasian patients, making the LDMF more suitable. However, despite its benefits, capsular contracture has been reported in patients with a tissue expander or implant, as well as aesthetic dissatisfaction with the donor site.¹¹

In this study, free flaps became an increasingly common choice for the procedure. Because of its good vascularization, faster healing and various other resource-related characteristics, free flaps are used more and more widely as microsurgical techniques improve. Inserting a tissue expander or random-pattern flap was flexibly employed as an option to avoid intensive operations and/or excessively large defects on the donor side. Furthermore, the expanded flap not only provides well-vascularized tissues for radiation-induced wounds with minor complications but also improves the aesthetic outcomes.

The LOS was longer in this study than in previous research, for a few reasons.⁷ Firstly, we controlled the base of the ulcer by two methods (partial and total excision). For first-degree and second-degree ulcers, both the necrotic area and the entire affected area were completely excised, while the other ulcers underwent partial excision because of the presence of highly vascular areas or ribs below the wound. When we could not completely control the base of the ulcer, we often left the drain tube in for a longer time. Secondly, the longer LOS reflected infection control measures in the absence of culture evidence due to institution-specific circumstances. Finally, a few other factors can seriously affect wound healing, including hypertension, the patient’s position after the operation, and splinting.

Conclusion

Our findings indicate that single reconstruction is a valuable option for managing radiation-induced ulcers. Drawing upon an armamentarium containing various types of flap, surgeons should choose the most suitable immediate reconstructive method for a radiation-induced ulcer to obtain the optimal treatment outcomes without complications or recurrence, thereby significantly improving patients’ quality of life.