BURN SURGERY AND RESEARCH

Keloid Excision and Adjuvant Treatments

A Network Meta-analysis
Charalampos Siotos, MD,* Akachimere C. Uzosike, BA,* Hwanhee Hong, PhD,† Stella M. Seal, MLS,‡
Gedge D. Rosson, MD,* Carisa M. Cooney, MPH,* and Damon S. Cooney, MD, PhD*

groups are more frequently affected, particularly African Americans

Background: Keloid disease treatment continues to be unsatisfactory with high recur-
and Asians.7
rence rates. We evaluated the literature regarding the effectiveness of keloid excision
Although keloids and hypertrophic scars are not life-threatening,
with various adjuvant treatments following surgery and assessed recurrence rates.
great morbidity can be associated with these pathologies. A recent study
Methods: We systematically searched databases through November 2016. We
provides evidence that patients with keloid scars have lower emotional
performed pairwise meta-analyses and Bayesian network meta-analyses on the
and mental health quality-of-life scores in comparison to the reference
number of recurrences.
keloid-free group. Pruritus and pain were among the significant factors
Results: Following screening, 14 studies including 996 patients with various
affecting patient scores.8 Following intramarginal keloid excision and
types of keloids were eligible for inclusion. Patients were categorized based on
steroid injection, quality-of-life scores were significantly improved in
the receipt of surgery and the type of adjuvant treatment employed afterward.
recurrence-free patients, whereas patients with recurrences did not achieve
Paired meta-analysis (6 meta-analyses) showed that “excision + 1 adjuvant drug”
the same improvement.9
led to statistically significantly higher odds of recurrence compared to “excision +
Research has revealed that the pathophysiology of the disease lies
radiation” (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.35–7.67).
in the wound healing process10 and is the result of chronic inflammation
Based on the network meta-analyses, the ORs of keloid recurrence following var-
within the reticular dermis.11 Excess deposition of extracellular matrix by
ious treatments compared to no excision were as follows: “excision + pressure,
fibroblasts or decreased degradation and remodeling by metalloprotein-
0.18 (95% CI, 0.01–7.07); excision + 2 adjuvants drugs, 0.47 (95% CI, 0.02–12.82);
ases of the matrix result in keloid and hypertrophic scar formation.12
excision + radiation, 0.39 (95% CI, 0.04–3.31); excision + skin grafting, 0.58
Animal keloid models exhibit an exaggerated inflammatory response
(95% CI, 0.00–76.10); excision + 1 adjuvant drug, 1.76 (95% CI, 0.17–21.35);
to any skin trauma, including increased transforming growth factor β
and excision only, 2.17 (95% CI, 0.23–23.95).
(TGF-β), vascular endothelial growth factor, and connective tissue
Conclusions: According to our results, “excision + radiation” had significantly
growth factor.13
better outcomes than excision alone. “Excision + pressure” had better outcomes
Despite remarkable medical and surgical developments over the
than excision + any other treatment modality, and excision + nonradiation adjuvant
past century, the treatment of keloids remains controversial.14 Medical
therapies were also better than “excision only,” although these findings did not
regimens introduced for the treatment of keloids/hypertrophic scars are
reach statistical significance.
intralesional corticosteroids,15 antineoplastic drugs such as 5-fluorouracil
Key Words: keloid, meta-analysis, reconstruction, review, scar (5-FU),16 silicone gel sheets,17 and pressure therapy.18 Interventional
(Ann Plast Surg 2019;83: 154–162)
treatments include surgical excision, cryotherapy, radiation, and laser
therapy.19 Although various treatments have been employed either as
single regimen or as combined regimen,20 recurrence rates remain high
K eloids and hypertrophic scars are chronic skin pathologies that affect
approximately 15 new patients per 10,000 people every year.1 These
conditions may result from skin trauma including any injury, burn, sur-
and no criterion-standard therapy has been established.21 In light of this,
we sought to evaluate the success rates of different adjuvant treatments
gical procedure, or acne, or they may grow spontaneously in genetically employed immediately after surgical excision of keloids by conducting
predisposed patients.2 Keloids are created by deposition of collagen, a systematic review and network meta-analysis. This type of analysis
glycosaminoglycans, and acidic mucopolysaccharides that normally enabled us to simultaneously take into account and compare directly and
exist in the skin.3 In the case of keloids, this deposition is disorganized, indirectly the recurrence rates among multiple treatment modalities.22
in excess, and enriched in collagen type I rather than collagen type III.4 To our knowledge, this is the first network meta-analysis assessing
Hypertrophic scars present with the same characteristics as keloids but the effects of different adjuvant treatments after surgical excision for the
are milder because, unlike keloids, hypertrophic scars do not grow beyond management of keloids.
scar borders.4 Additionally, keloids tend to recur and do not regress.5 In
both cases, the development of keloids or hypertrophic scars often runs MATERIALS AND METHODS
in families, implying a genetic background to the disease.6 Specific ethnic
Literature Search
We conducted the present systematic review and meta-analysis
Received November 2, 2018, and accepted for publication, after revision March 4,
2019.
using the guidelines suggested by the Preferred Reporting Items for Sys-
From the *Department of Plastic & Reconstructive Surgery, Johns Hopkins University tematic Review and Meta-analyses.23 Additional guidelines for conducting
School of Medicine; and †Bloomberg School of Public Health and ‡Welch network meta-analyses were employed.24,25 We did not register a protocol.
Medical Library, Johns Hopkins University, Baltimore, MD. The present study conforms to the Declaration of Helsinki, and approval
Conflicts of interest and sources of funding: none declared.
Reprints: Damon S. Cooney, MD, PhD, Johns Hopkins University School of Medicine,
by the institutional review board was waived. A qualified informaticist
601 N Caroline St, Baltimore, MD 21205. E-mail: dcooney2@jhmi.edu. (S.M.S.) performed the search of the databases PubMed, EMBASE,
Supplemental digital content is available for this article. Direct URL citations appear in Cochrane Library, and Scopus through November 29, 2016, using specific
the printed text and are provided in the HTML and PDF versions of this article on terms available as online supplemental material (Table, Supplemental
the journal’s Web site (www.annalsplasticsurgery.com).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Digital Content 1, http://links.lww.com/SAP/A364). We included studies
ISSN: 0148-7043/19/8302–0154 with an experimental or observational controlled design that were pub-
DOI: 10.1097/SAP.0000000000001951 lished in English. We did not apply restrictions on number of participants,

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Annals of Plastic Surgery • Volume 83, Number 2, August 2019
range of follow-up, type of adjuvant treatment, or date. Reviews, un-
controlled studies, animal studies, conference proceedings, and letters
to the editor were excluded. Two authors (C.S., A.U.) independently
completed article selection based on eligibility criteria. Discrepancies were
arbitrated by the senior author (D.S.C.). A flow diagram of the literature
search is presented in Figure 1.
Data Extraction
We categorized the different regimens into 7 broad categories to
ensure sufficient sample sizes in each group and subsequently the
power to draw conclusions. Categories were designed in advance to
minimize introduction of heterogeneity in our analysis and were as fol-
lows: (1) no excision group: all patients who received either medical or
radiological therapy but no surgical therapy; (2) excision-only group:
patients who received only excision and no adjuvant treatment (neither
medical nor radiological); (3) excision + 1 adjuvant drug group: all patients
who underwent keloid excision and 1 adjuvant medical treatment (eg,
intralesional injections of steroids, interferon [IFN], calcium-channel
blockers [verapamil], or colchicine); (4) excision + 2 adjuvant drug
group: patients who received excision and 2 different classes of drugs
as adjuvant treatment; (5) excision + radiation therapy group: patients
who underwent excision and radiation therapy with or without medical
treatment; (6) excision + pressure: patients who underwent excision and
then pressure therapy; and (7) excision + skin grafting: patient who
underwent excision and then skin grafting on top of the excision site.
Finally, within the excision + 1 adjuvant drug group, we extracted infor-
mation on the drug used and formed 2 groups: one that received steroid
injections and one that received IFN. Two authors (C.S., A.U.) independently
FIGURE 1. Flow diagram of literature search.
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Keloid Excision and Adjuvant Treatments
extracted the information of interest. These included year of publication,
study design, number of patients, demographics of patients such as
race, treatment regimen, number of recurrences, previous treatments,
location of keloid, and duration of follow-up after each treatment.
Quality Assessment
The first author (C.S.) assessed the methodological quality of the
included studies, by using two tools. The Jadad score26 was used for ex-
perimental studies (eg, trials) and the MINORS (Methodological Index
for Non-Randomized Studies) criteria27 were used for observational
studies. For studies that the full-text article was not available, we did
not perform a quality assessment.
Statistical Analysis
Paired meta-analysis was initially performed to evaluate those
studies that had directly evaluated the same treatment regimens. We
conducted the statistical analysis using Review Manager, version 5.3
(The Cochrane Collaboration, Copenhagen).28 We preset confidence
intervals (CIs) at 95% and the level of statistical significance at P < 0.05.
We calculated odds ratio (OR) and 95% CI for all outcomes using the
Mantel-Haenszel method random-effects model (REM) because of
considerable heterogeneity across the studies' populations.29 We tested
for statistical heterogeneity with the Q statistic, generated by χ2 test and
measured the extent of the heterogeneity based on the I2 measure-
ment.30 We considered heterogeneity values for I2 values of less than
50% as low, 50% to 75% as medium, and greater than 75% as high.30
We did not formally assess publication bias and funnel plot asymmetry
www.annalsplasticsurgery.com 155
 156
TABLE 1. Characteristics of Patients in the Included Studies
Siotos et al

Quality Percent of
Assessment Period of African Anatomic
Study, Year Study Design Score Recruitment Location Sample Size Age, y American Location Lesion Size, cm Etiology Prior Treatments
39
Nason, Retrospective 10* N/S USA 49 Patients N/S N/S N/S N/S N/S N/S
1942 cohort (51 keloids)
Sclafani Prospective, 3† 1991–1992 USA 25 Females, Mean, 28 64.5% Earlobe (100%) N/S Ear piercing Surgery or steroid
et al,40 randomized 6 males (97%) injection
1996
Berman and Retrospective 15* 1993–1996 USA 66 Females, Range, 8–61 88% Earlobe 99 (86%), Range, Ear piercing Intralesional TAC
Flores,41 cohort 8 males neck (2.4%), 0.5–3.0 (50%), trauma injections (83%)

www.annalsplasticsurgery.com
1997 chest (1.6%), (9%), chicken
back (0.8%), pox (3%),
extremities surgery (5%),
(0.8%), other: burn (1.4%),
head (9%) unknown
(31.6%)
Guix,42 Prospective 13* 1991–1998 Spain 134 Females, Mean, 42 0.6% Face (45.6%), Mean length: Surgery or N/S
2001 cohort 35 males trunk (43.2%), 4 .2cm, trauma
extremities mean width:
(11.2%) 1 .8 cm
Jackson Retrospective 16* N/S USA 14 Females, Mean, 25; 75% Ear (100%) Mean, 2.6; Ear piercing N/S
et al,43 cohort 10 males range, range, (79.2%),
2001 7–64 0.5–6 trauma
(12.5%),
surgery (8%)
D'Andrea Prospective, 13* N/S Italy 16 Females, Range, 0% (White Back (22.7%), 2–6 N/S N/S
et al,44 cohort 28 males 22–45 100%) deltoid (13.6%),
2002 sternum (13.6%)
Hatamipour Prospective, 2† 2004–2008 Iran 30 Females, Range, 0% (Middle Back or abdomen Range, 2–6 N/S N/S
et al,45 randomized 20 males 22–45 Eastern (40%), sternum
2011 100%) (38%), deltoid
(10%)
Patel,46 Retrospective 16* 2000–2008 USA 10 females, Mean, 11; 41% N/S N/S Burn (100%) Multiple
2012 cohort 24 males range,

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1–21
Kim et al,47 Retrospective Not estimable 2005–2011 South 36 Females Mean (SD), 0% (Asian Ear (100%) N/S Ear piercing N/S
2012 cohort (no full text Korea 23.8 (8.5) 100%) (100%)
available in
English)
Carvalho Retrospective 13* 2006–2009 Brazil 3 Females, Range, 0% (white Ear (100%) N/S Surgery (100%) N/S
et al,48 cohort 6 males 9–27 100%)
2012
Ozaki Prospective, Not estimable N/A Japan N/A N/A N/A N/A N/A N/A N/A
et al,49 cohort (no full text
2010‡ available)
Cao et al,50 Prospective, Not estimable N/A China N/A N/A N/A N/A N/A N/A N/A
2015‡ randomized (no full text
available)

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Annals of Plastic Surgery • Volume 83, Number 2, August 2019
Annals of Plastic Surgery • Volume 83, Number 2, August 2019 Keloid Excision and Adjuvant Treatments

therapy (17.2%), as funnel plot asymmetry testing is not recommended for meta-analyses

steroid injection
with fewer than 10 studies each.31
(24.1%), laser

excision with
intralesional
Prior excision

Network meta-analysis was conducted to collectively evaluate

N/S

(6.9%), idiopathic (17.2%)

the role of all the regimens in comparison to the rest by conducting both
direct and indirect comparisons. We fitted a Bayesian random-effects
network meta-analysis model to account for treatment effect heterogeneity
across studies.32,33 We assumed that the magnitude of the effect heteroge-
neity is the same for every treatment (ie, homogeneous REM) and that
surgery (26.1%),
Piercing (38.9%),

evidence from direct and indirect comparisons is the same (ie, consis-
(17.7%), acne
(7.9%), burn
vaccination

tency model). We also assessed inconsistency and discrepancy of direct

N/S

trauma or

and indirect evidence, using a node-splitting approach.34 We ranked

(2.5%)

treatments using the “Surface under the Cumulative Ranking” curve

(SUCRA) value.35 SUCRA is the percentage ratio between the surface
underneath the cumulative ranking curve and the entire space in each
7.7 (group A),

plot. A larger SUCRA value indicates treatments with a higher rank.

7.2 (group B)

To obtain the cumulative ranking probabilities, we first calculated the

Mean height,

ranking probabilities for each treatment at any possible ranks (eg, prob-
N/S

ability of being the best, second best, or worst) and then calculated the
cumulative sum of these ranking probabilities (eg, probability of being
among the top 2 treatments). Markov chain Monte Carlo (MCMC) algo-
rithms were used to estimate treatment effects. We also used the “gemtc”
(9.4%), abdomen/
perineum (5.4%),
face/neck (1.0%)
shoulder/deltoid

R package, which recalls JAGS in R for MCMC sampling.36 We em-

Face (59.8%), ear

(17.7%), chest
(23.4%), lip

ployed 4 parallel chains and obtained 50,000 samples after discarding

extremities
Ear (42.4%),

20,000 samples in each chain. Convergence of MCMC chains was

(24.1%),
(18.7%)

checked using the Gelman and Rubin diagnostic37 and trace plots.38

RESULTS
Median, 15 0% (Asian
(interquartile 100%)

Literature Search
100%

The initial search after removing duplicates revealed 3187 unique

titles that were screened for eligibility by title and abstract. Seventy- four
were considered eligible and were selected for evaluation based on the
full-text articles. Finally, 14 were included in our meta-analysis. No fur-
12–18)
Mean, 27

range,

*MINORS criteria for quality assessment of observation studies was used (range of scores, 0–24).

ther articles were identified by screening reference lists of other included

studies. The quality of the 14 selected studies was evaluated, and the re-
sults are available in Table 1. Table 1 also contains basic relevant infor-
mation regarding the patients included in each study and prior
167 females,
48 Females,
59 males

36 males

treatments received. Table 2 presents the treatments used and related

†Jadad quality assessment score for clinical trials was used (range of scores, 0–5).

recurrence rates.

Outcomes
Korea

We performed 6 paired meta-analyses, comparing different

2005–2006 Nigeria

2002–2012 South

treatment dyads:
(1)No excision versus excision only: Two studies39,52 were included,
resulting in 25 patients in the nonexcision group and 15 in the excision-
only group. Odds for recurrence were lower for the nonexcision group
at the marginally statistically significant level (OR, 0.25; REM; 95%
CI, 0.06–1.00; P = 0.05; I2 = 0%, Fig. 2).
(2)Excision only versus excision + 1 adjuvant drug: Five stud-
ies40,41,47,48,52 were included, resulting in 78 patients among the
excision-only group and 192 among the excision + 1 adjuvant drug
15*

16*

group. Odds for recurrence were greater for the excision-only group
but were not statistically significant (OR, 1.41; REM; 95% CI,
0.78–2.54; P = 0.26; I2 = 0%; Fig. 3).
(3)Excision only versus excision + radiation: Six studies39,40,47–49,51
Retrospective
Aluko-Olokun Prospective

were included, resulting in 119 patients among excision-only group

‡Full text not available.
cohort

cohort

and 127 among the excision + radiation group. Odds for recurrence
N/S, not specified.

were greater for the excision-only group and were not statistically
significant (OR, 3.59; REM; 95% CI, 0.56–22.96; P = 0.18;
I2 = 77%; Fig. 4).
Chang,52

(4)Excision + 1 adjuvant drug versus excision + 2 adjuvant drugs:

et al,51

Park and

Three studies43–45 were included, resulting in 60 patients among the

2014

2015

excision + 1 adjuvant drug and 66 among the excision + 2 adjuvant

drugs group. Odds for recurrence were greater among the patients

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Siotos et al Annals of Plastic Surgery • Volume 83, Number 2, August 2019

TABLE 2. Number of Keloid Recurrences Following Various Treatments, as Reported by the Included Studies

Excision + 1 Excision + 2 Excision + Excision + Excision + Skin

Study No Excision Excision Only Adjuvant Drug Adjuvant Drugs Radiation Pressure Grafting
Aluko-Olokun et al,51 2014 10/54 22/53
Berman and Flores,41 1997 22/43 41/81
Carvalho et al,48 2012 0/1 0/2 1/7
Guix,42 2001 3/22 5/147
Jackson et al,44 2001 2/13 5/19 0/8
Park and Chang,52 2015 1/5 1/3 14/66 3/89
Patel,46 2012 7/8 20/26
D'Andrea et al,44 2002 16/22 2/22
Hatamipour et al,45 2011 5/25 1/25
Sclafani et al,40 1996 1/3 4/12 2/16
Kim et al,47 2012 12/28 6/31 0/12
Nason,39 1942 6/20 8/12 3/19
Cao et al,50 2015 13/30 6/31
Ozaki et al,49 2010 5/21 0/20

FIGURE 2. Forest plot for no excision versus excision only.

FIGURE 3. Forest plot for excision only versus excision + 1 adjuvant drug.

FIGURE 4. Forest plot for excision only versus excision + radiation.

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Annals of Plastic Surgery • Volume 83, Number 2, August 2019 Keloid Excision and Adjuvant Treatments

FIGURE 5. Forest plot for excision + 1 adjuvant drug versus excision + 2 adjuvant drugs.

FIGURE 6. Forest plot for excision + 1 adjuvant drug versus excision + radiation.

FIGURE 7. Forest plot steroid versus IFN as adjuvant treatments following excision.

FIGURE 8. Network graph of the 14 studies. The size of the node is proportional to the number of subjects contributed to that drug.
Each edge connecting 2 nodes represents a direct comparison between the 2 drugs. The thickness of the edge is proportional to the
number of studies investigating the relationship.

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Siotos et al Annals of Plastic Surgery • Volume 83, Number 2, August 2019

who received excision and 1 additional medical treatment. However,

Posterior means of OR between column and row (95% Bayesian credible intervals) under the Bayesian REM are reported. Odds ratio of less than 1 favors the treatment in the column, and OR greater than 1
1.22 (0.01–128.38)
1.52 (0.01–143.17)
3.23 (0.01–670.48)
0.58 (0.00–76.10)
0.27 (0.00–22.87)
0.33 (0.00–20.42)
Excision + Skin
this difference was not statistically significant (OR, 4.34; REM; 95%

Grafting
CI, 0.38–49.20; P = 0.24; I2 = 79%; Fig. 5).
(5)Excision + 1 adjuvant drug versus excision + radiation: Five stud-
ies40,43,47,48,50 were included, resulting in 88 patients among the exci-
sion + 1 adjuvant drug group and 74 among the excision + radiation
group. Odds for recurrence were significantly higher for the exci-
sion + 1 adjuvant drug group (OR, 3.22; REM; 95% CI, 1.35, 7.67;
P = 0.008; I2 = 0%; Fig. 6).

0.38 (0.01–18.75)
0.46 (0.02–16.58)

0.31 (0.00–89.93)
0.18 (0.01–7.07)
0.08 (0.00–2.41)
0.10 (0.00–2.71)
(6)Steroids versus IFN in the excision + 1 adjuvant drug group: Two

Excision +
Pressure
studies41,53 were included resulting in 91 patients who received ste-
roids as adjuvant treatment and 29 who received IFN among patients
of the excision + 1 adjuvant drug group. Odds for recurrence were
similar among patients of the 2 groups (OR, 0.99; REM; 95% CI,
0.03, 36.31; P = 1.00; I2 = 92%; Fig. 7).
We also investigated the 7 treatments presented in the 14 studies

2.16 (0.06–66.42)
0.66 (0.01–81.29)
0.39 (0.04–3.31)

0.22 (0.04–1.04)
0.18 (0.03–0.79)

0.82 (0.05–9.84)
in a network fashion (Fig. 8). The total number of direct comparisons

Excision +
Radiation
was 12. Out of 14 studies, 8 studies compared 2 treatments; 5 studies
compared 3 treatments; 1 study compared 4 treatments (Table 2). Most
subjects underwent excision + radiation (313 of 996), and the fewest
subjects underwent excision + skin grafting (26 of 996).
Odds ratio estimates and the associated 95% CIs in comparison
to no excision were calculated (Table 3) and were as follows: excision +
pressure” 0.18 (0.01–7.07); excision + 2 adjuvant drugs, 0.47 (0.02–12.82);

2.64 (0.05–149.46)
0.82 (0.01–134.56)
0.47 (0.02–12.82)

1.22 (0.10–20.23)
0.22 (0.02–3.25)
0.27 (0.03–2.41)
Adjuvant Drugs
excision + radiation, 0.39 (0.04–3.31); excision + skin grafting, 0.58

Excision + 2
(0.00–76.10); excision + 1 adjuvant drug, 1.76 (0.17–21.35), and exci-
sion only, 2.17 (0.23–23.95). The only statistically significant difference
identified was for the lower rates of recurrences for patients who received
excision + radiation, in comparison to excision only. SUCRAvalues were
calculated based on the cumulative ranking probability curve of each
treatment (Figure, Supplemental Digital Content 2, http://links.lww.
com/SAP/A365). The values, ordered from the most effective treatment

9.85 (0.37–290.32)
3.02 (0.05–307.35)
1.76 (0.17–21.35)

4.56 (0.97–27.77)
3.72 (0.41–32.66)
0.81 (0.15–4.24)
Adjuvant Drug

to the least effective, were excision + pressure, 79.2; excision + radiation,

TABLE 3. OR Estimates for Keloid Recurrence Obtained From Network Meta-analysis

Excision + 1

70.7; excision + 2 adjuvant drugs, 62.2; excision + skin grafting, 54.0; no

excision, 42.0; excision + 1 adjuvant drug, 23.6; and excision only, 18.4.
Gelman diagnostic statistics and trace plots are available as online sup-
plemental material (Document, Supplemental Digital Content 3, http://
links.lww.com/SAP/A366). 12.17 (0.41–386.06)
3.74 (0.04–496.71)
5.61 (1.27–32.04)
2.17 (0.23–23.95)

4.59 (0.31–64.78)
1.23 (0.24–6.50)
Excision Only

DISCUSSION
Keloids and hypertrophic scars are difficult to treat and often re-
cur following treatment. Excision is commonly used because it yields
the most rapid visible reduction of the keloid. However, as with other
treatments, excision is associated with a high rate of recurrence. Although
favors the treatment in the row. Significant ORs are in bold.

the risk of recurrence is thought to be lower when combined with an ad-

5.59 (0.14–200.34)
1.72 (0.01–294.12)
2.13 (0.08–46.20)
2.59 (0.30–24.31)
0.46 (0.04–4.30)
0.57 (0.05–5.74)

juvant therapy, there is no consensus regarding which adjuvant therapy

No Excision

best prevents recurrence. In this study, we sought to compare the effect

of various adjuvant modalities in treating keloids.
Of the multiple paired comparisons that we performed, exci-
sion + radiation proved more effective at reducing the odds of keloid re-
currence than excision + 1 adjuvant drug. This inference was drawn
from 5 studies comparing a total of 162 patients. Of the groups we compared,
this was the only one in which we found a significant difference in recur-
Excision + 2 adjuvant drugs
Excision + 1 adjuvant drug

rence rate. In the comparison group, the most commonly used nonradiation
Excision + skin grafting

adjuvant modalities were steroid injections. However, according to the

Excision + radiation

paired meta-analysis excision + radiation did not consistently outperform

excision + pressure

other modalities. The results of our paired meta-analysis agree with the
results of the network meta-analysis, according to which excision + radi-
Excision only
No excision

ation was proven superior at preventing recurrences in comparison to

excision only. In addition, excision + pressure was found to lead to less
recurrences than the other treatment modalities; however, this differ-
ence was not statistically significant.

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Annals of Plastic Surgery • Volume 83, Number 2, August 2019
Radiation therapy has been utilized for treating keloids for over a
century.54 The effectiveness of postexcision radiation therapy in reducing
keloid size has been demonstrated by multiple studies.55–58 A 2015 study
found that radiation affects keloid formation by decreasing fibroblast
proliferation through inhibition of histamine release from mast cells
and suppressing collagen synthesis through inhibition of TGF-β1.56
The most commonly used forms of radiation therapy for keloids are
brachytherapy and electron beam radiation. In a retrospective review
of 612 patients with 892 keloids treated between 1992 and 2006 with
postexcision brachytherapy, Viani et al59 reported a recurrence-free re-
sponse rate of 87.6% with a median follow-up of 61 months. These authors
additionally reported that keloids secondary to burns and those that pre-
viously received any treatment were the most likely to recur following
excision and brachytherapy. Ogawa et al60 reported a 4% recurrence
rate at 18 months in 174 lesions among 145 patients who underwent ex-
cision and radiation. However radiation therapy is associated with adverse
effects that must be considered, such as carcinogenesis (eg, especially
fibrosarcoma, thyroid carcinoma, and breast carcinoma). A review by
Ogawa et al54 reported a very low rate of carcinogenesis attributable
to radiation therapy for keloids. Radiation therapy is regarded as a safe
option when carefully applied in select patients.
Excision-induced injury can often start the process of keloid
recurrence. In this study, the results from the comparison in dyad 1 cor-
roborates this point. Current thinking in the field is that recurrence rates
can be reduced when excision is combined with pre-excision or
postexcision adjuvant therapies. There is currently no standard of care
for combination treatment regimens involving excision. Possible adjuvant
therapies include intralesional injection of corticosteroids, radiation,
silicone sheet gel sheets, pressure garments, and skin grafting. These
therapies can also be used as monotherapies.
Excision therapy often results in reduction of scar size and volume,
symptomatic relief of pain and pruritus, and cosmetic improvement.
Intralesional injection of corticosteroids, compression, and silicone
sheeting may reduce scar volume by as much as 50% in some patients.61
Corticosteroids work by inhibiting fibroblast proliferation and reducing
collagen and glycosaminoglycan synthesis. Intralesional injection of tri-
amcinolone acetonide is the most commonly used treatment for keloids
and hypertrophic scars.62 The investigators reported, on average, an
83% reduction in pruritus and pain among 94 patients with 109 keloids
and a reduction in size by 4 weeks following intralesional corticosteroid
injection. While these rates appear to be promising, intralesional injec-
tions are associated with multiple adverse effects. These include dermal
atrophy and hypopigmentation or hyperpigmentation. Hypopigmentation
is particularly seen in African Americans and individuals with darker skin
tones. For some patients who fail intralesional corticosteroid therapy,
5-FU is used instead; 5-FU has been shown to induce macrophage ap-
optosis and inhibit TGF-β signaling,63 which is important for type I
collagen synthesis and keloid formation.
Our study is not without limitations. The small sample size in the
literature we found limited our ability to discern more precise treatment
effects of each tested modality. Because of this, we cannot conclusively
state that excision + radiation is superior to the other modalities we
analyzed, although the analysis shows a trend toward this conclu-
sion. Additionally, despite the fact that keloids affect millions of
people worldwide, there is an ostensible lack of randomized trials
that severely limits our ability to draw safe conclusions; the area of
keloid therapy and care is in great need of higher-level evidence
studies. A large variety of treatment modalities for keloids now exist.
This is beneficial to patients, whose keloids manifest themselves in a
wide variety of forms and etiologies and thus require tailored thera-
pies. This large variety, however, adds to the challenge of identifying
the treatments that are most effective for reducing the risk of recur-
rence. We recommend future randomized controlled trials testing a
small set of treatments as a strategy to better delineate the effectiveness
of keloid therapies.
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Keloid Excision and Adjuvant Treatments
CONCLUSIONS
We employed the novel statistical tool of network meta-analysis
in order to evaluate the effect of different adjuvant treatments following
keloid excision. “Excision + radiation” seems to have significantly less
recurrences than “excision only” or “excision + 1 adjuvant drug.” However,
future randomized trials are necessary in order to draw more confident
conclusions and help guide clinical decision making.
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