Multimodal Keloid Therapy with Excision, Application of Mitomycin C, and Radiotherapy

Keloids are benign, firm, fibroproliferative growths

occurring in the dermis and adjacent subcutaneous

tissue as a result of dermal injury. Many keloid

treatment modalities exist, but poor results are typ-

ically achieved with even radical monotherapy

treatment options. Two promising forms of multi-

modal therapy for the treatment of keloids,

detailed in recent meta-analyses,1,2 are resection

with adjuvant radiotherapy3 and resection with

adjuvant topical chemotherapeutic agents,4 includ-

ing mitomycin C.5 A review of the literature

reveals that both methods, although each moder-

ately effective on its own, have not been used in

combination for the treatment of medium-sized to

large (>5 cm) keloids. It is the experience of the

authors that multimodal therapy with resection,

application of mitomycin C, and radiotherapy rep-

resents an excellent algorithm for the treatment of

such keloids.

Technique and Results

Our triple therapy has been used in our clinic on

seven separate keloids, and we present two repre-

sentative cases to highlight this technique. Patient

A, a 32-year-old man, and Patient B, a 40-year-old

woman, were chosen from dermatology outpatients

to undergo triple therapy. Both patients were

African American. Patient A presented with a 6- by

5-cm keloid on his center chest (Figure 1). Patient

B presented with a 6.5- by 2-cm keloid at the base

of her left neck (Figure 2). Each patient had a his-

tory of treatment with established keloid therapies,

including triamcinolone injections, cryotherapy,

and silicone sheeting, all with poor results.

Each keloid was photographed before surgery, and

local anesthetic was injected under and around the

keloid. The keloid was then shave-removed level

with the surrounding skin, and hemostasis was

achieved. A gauze pad, cut to conform to the shape

of the wound, was soaked in mitomycin C 1 mg/

mL and applied to the wound for 3 minutes. The

wound was then covered, and the patient was sent

to the Radiation Oncology Department for same-

day adjuvant radiotherapy.

In the Radiation Oncology Department, the patient

underwent an initial radiotherapy session using

custom lead cut-outs. The patient then returned on

postoperative days 2 and 3 to complete additional

radiotherapy fractions. Each fraction consisted of

Figure 1. Patient A with 6- by 5-cm keloid on center chestbefore therapy.

Figure 2. Patient B with 6.5- by 2-cm keloid at the base ofleft neck before therapy.

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DERMATOLOGIC SURGERY480

6 Gy of 6-MeV en face electrons, for a total of

18 Gy completed within 72 hours postoperatively.

At 3 weeks after surgery, the patients surgical sites

were examined, and mitomycin C 1 mg/mL was

applied on soaked gauze for 3 minutes as before.

The patients then followed up in the Dermatology

Department 1, 3, and 6 months after treatment;

during the 6-month postoperative visit, photo-

graphs were taken of their treatment sites

(Figures 3 and 4), and the patients were asked to

rate their satisfaction on a linear analogue scale

from 1 (least satisfied) to 5 (most satisfied).

Triple therapy with excision, application of mito-

mycin C, and radiotherapy proved effective in the

treatment of our patients keloids. Only limited,

focal recurrence of keloid tissue was noted in the

follow-up period of up to 2 years. Patient A noted

a transient dermatitis after treatment of her third

keloid, but no other significant adverse effects were

noted. Intralesional triamcinolone and silicone

sheeting were also used in focal areas of the keloid

after triple therapy to assist with further flattening

of the lesion, although the use of these agents on a

limited surface area was unlikely to be a significant

factor in the overall reduction in recurrence of the

lesions, given the lack of response previously.

Overall, both patients were highly satisfied with

the results of their treatment, with Patient A

choosing 4 and Patient B choosing 5 on the linear

analogue scale.

Discussion

Keloids are formed by intrinsically normal poly-

clonal fibroblasts responding to an abnormal

extracellular signal.1 They are characterized by

expansion beyond the boundaries of the original

injury, do not regress spontaneously, and often

recur after excision. Patients often report pruritus,

tightness, and tenderness at the keloid site. The

sheer number of available treatment modalities

suggests that no single definitive treatment option

exists, and providers may often improvise multi-

modal therapy based on the size of the keloid and

overall result desired by the patient.

Resection with adjuvant radiotherapy has been a

long-standing treatment of keloids.3 The mecha-

nism of action is thought to involve a reduction of

epithelial proliferation through induction of fibro-

blast apoptosis.1 A 2005 meta-analysis3 demon-

strated that the recurrence rate of keloids could be

driven below 10% by increasing the biologically

effective dose (BED) of radiotherapy above 30 Gy.

Also, best results were achieved when radiotherapy

was initiated within 48 hours of surgery. We

achieved the recommended BED to the surgical

site by using three fractions of 6 Gy and began

radiotherapy immediately after surgery and appli-

Figure 3. Patient A center chest after therapy.

Figure 4. Patient B base of left neck after therapy.

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40 : 4 :APRIL 2014 481

cation of mitomycin C, with all radiotherapy treat-

ments completed within 72 hours. Exposure of

surrounding tissue to radiation was minimized

using custom lead cut-outs manufactured

postoperatively.

An antineoplastic agent derived from Streptomyces,

mitomycin C inhibits DNA synthesis by cross-link-

ing strands of the DNA double-helix, preventing

tissue proliferation.4 Historically, mitomycin C has

proven successful in the fields of ophthalmology

and tracheal surgery.5 Early case reports in the use

of resection and adjuvant mitomycin C to treat

keloids were equivocal,1 although the concentra-

tion of mitomycin C used in these early case

reports was low (0.4 mg/mL). Gupta and Narang5,

in a 2010 review, successfully treated 26 pinna

keloids by applying a higher concentration of mito-

mycin C (1 mg/mL) immediately postoperatively

and 3 weeks after surgery. We have also found

success with a higher concentration and staggered

application of mitomycin C.

Conclusion

Keloids are commonly encountered and notoriously

difficult to treat, representing a therapeutic

dilemma. Although many keloid treatment modali-

ties are available, monotherapy has historically

yielded poor results. The authors acknowledge that

the number of patients treated in this series is

small, and the follow-up period is limited; to fur-

ther validate these results, more patients should be

treated with the above protocol, and the follow-up

period should be extended to at least 5 years to

monitor long-term results. Multimodal therapies of

resection with adjuvant radiation and resection

with adjuvant mitomycin C have each shown

moderate success; the authors propose that

combination of these established therapies into a

triple therapy of resection with adjuvant mitomycin

C and radiotherapy needs to be further explored

and may represent a promising treatment algorithm

for this difficult disease.

References

1. Naylor M, Brissett A. Current concepts in the etiology

and treatment of keloids. Facial Plast Surg 2012;28:

50412.

2. Sidle D, Kim H. Keloids: prevention and management. Facial

Plast Surg Clin North Am 2011;19:50515.

3. Kal H, Veen R. Biologically effective doses of postoperative

radiotherapy in the prevention of keloids. Strahlenther Onkol

2005;181:71723.

4. Shridharani SM, Magarakis M, Manson PN, Singh NK, et al.

The emerging role of antineoplastic agents in the treatment of

keloids and hypertrophic scars. Ann Plast Surg 2010;64:35561.

5. Gupta M, Narang T. Role of mitomycin C in reducing keloid

recurrence: patient series and literature review. J Laryngol Otol

2011;125:297300.

MATTHEW WILLETT, MD, MC USN

KENT HANDFIELD, MD, MC USN

JASON MARQUART, MD, MC USA

Walter Reed National Military Medical Center

Bethesda, Maryland

The views expressed in this manuscript are those of the

authors and do not reflect the official policy of the Depart-

ment of Army/Navy/Air Force, Department of Defense, or

U.S. government.

Transient Median and Ulnar Neuropathy Associated with a Microwave Device for Treating Axillary

Hyperhidrosis

Microwave-based devices are recently developed

technology to treat hyperhidrosis by selectively

heating the interface between dermis and subcu-

taneous fat. A few studies using a microwave-

based device for hyperhidrosis13 have

demonstrated significant sweat reduction without

serious complications. We report a case of tran-

sient median and ulnar neuropathy associated

with treatment of hyperhidrosis with the micro-

wave-based device.

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