Page 22 - Read Online

Xu et al. Radiation therapy in keloids treatment

platelet-derived growth factor (PDGF)-α receptor were strategies emphasized on 5 major treatment modality,
all reported in previous studies. Alterations of these including intralesional corticosteroid injection,
[8]
growth factors secretion were believed to be pivotal cryotherapy, surgical manipulation, radiotherapy and
for scarring process. Keloid-derived fibroblasts were laser therapy. Intralesional injections started since
reported more sensitive to several key growth factors 1960s, but demonstrating various but limited clinical
like TGF-β1, PDGF and IGF-1 compared to normal outcome. The suppression effect of topical inflammation
fibroblasts, which might explain the overproduction is considered the basis of intralesional corticosteroid
of collagen by keloid-derived fibroblasts. Moreover, injection. [17] Diminished collagen or extracellular
[9]
other than the collagen-producing cells fibroblasts, matrix and inhibition of fibroblasts migration were
keratinocytes isolated from keloid formation also both reported. However, the response rate was quite
were shown to have an aberrant behavior, especially uncertain, varying from 50% to 100%. [18,19] The control of
co-cultured with fibroblasts. Two vital cytokines were recurrence rate was also fluctuating, ranging from less
believed secreted from keloid-derived keratinocytes, than 10% to over 50%. [20,21] The most common adverse
the hypoxia-inducible factor-1α (HIF-1α) and release of effects included dermal atrophy, telangiectasia and
IL-1. [10] Some paracrine secretion by keloids were also local pain at the injection site. Another monotherapy
deemed as contributor to fibroblasts overgrowth and utilized accompanied with less trauma is cryotherapy,
collagen overproduction. [11] What’s more, melanocytes, which is believed to function through vascular damage,
mast cells and myofibroblasts were also all considered then anoxia and tissue necrosis. [22] The success rate
playing important roles in keloid scarring. [12,13] ranges from 32% to 74% when utilized for at least two
sessions. The adverse effects were quite similar to
As pathomechanism parallel to skin fibrosis, TGF-β intralesional corticosteroid injection. Botulinum toxin
was currently considered as one of the key regulators A injected intralesionally was considered as another
in keloid formation. TGF-β is the cytokine with a critical way to treat keloids, effective but better tolerated
wide variety of biological function implicated in other than intralesional steroid. [23] Besides, both intralesional
fibrotic disorders. Stimulation of cell proliferation and corticosteroid injection and botulinum toxin A injection
cellular differentiation made TGF-β family a very are combined with other therapies, especially radiation
important mediator in wound repair process, especially therapy. Furthermore, laser treatment is another
functioning in extracellular matrix production. In normal modality proved to be effective in controlling keloid
wound healing process or hypertrophic scarring, TGF- formation. Since the 1980s, multiple laser treatment
β’s activity will finally regress accompanied with wound modalities were introduced for keloids and hypertrophic
sites to be mature. However, in pathological process, scars, such as carbon dioxide laser and 585-nm
like keloid formation, TGF-β’s expression level and pulsed-dyelaser (PDL) laser. Notably, PDL laser is
activity remain sustainably upregulated. [14] SMAD nowadays considered the most effective among all
signal-transduction pathway, as the major downstream laser treatment utilized, especially initial hypertrophic
mediator of TGF-β, is believed to be dominant in keloid scars or primary keloids. [24] Laser treatment can
scarring process. Upregulated TGF-β diminishes the control keloid growth through generating ischemic
SMAD3 expression, which subsequently increase microenvironment. Besides, more and more treatment
procollagen gene expression and enhance ECM modalities were utilized, generating different clinical
deposition. [15] Except for TGF-SMAD pathway, other outcome. The major adjuvant preventative therapy
pathways involved in other fibrotic disorder or solid includes pressure, silicone gel sheeting, flavonoids.
tumors were also reported playing roles in keloid Some other drugs, especially chemotherapeutic or
formation at different levels, like p53 and mTOR. [16] immune suppressive drugs, such as 5-fluorouracil (5-
These pathways also provide us with substantial FU), Bleomycin, mitomycin C, botulinum toxin were
background when studying keloid’s response to also applied to treat keloids.
radiation.
Surgery and radiation therapy
MANAGEMENT OF KELOIDS Lastly, as one of the traditional treatment for keloids
and hypertrophic scars, surgical treated lesions alone
Management of keloids was considered a conundrum have a recurrence rate ranging from 45% to 100%.
without definitive optimal treatment strategies. A well- The surgery is believed to be another skin trauma
established treatment strategy was reported before, which potentially causes more damage than before.
mentioning a new emerging treatment strategy Then the combination therapy of surgery and other
comprised of surgical excision, radiation, corticosteroid post-operative treatment became popular around the
injection, laser and conservative multimodal therapy. world. Among these treatment modalities, combination
The current mainstream of current definitive treatment therapy of surgical excision and radiation therapy was

118 Plastic and Aesthetic Research ¦ Volume 4 ¦ July 28, 2017