Koki Nakamura, MD, Hiroyuki Irie, MD, PhD, Masahiro Inoue, MD

Koki Nakamura,
Hidenobu
Mitani,
MD, Hiroyuki
Irie, MD, PhD, Masahiro
Inoue, MD,
MD, Hiroshi Sunami, MD, and Shunji Sano, MD, PhD
Background:Even alter successful operations on children, unattractive postoperative scars are often distressing to patients and their parents. There are no
reports about fue factors affecting keloid or hypertrophic scar (HS) development alter congenital cardiac
surgery.
U Am Coll Surg 1997;185:218-223.
American College of Surgeons)
Keloid and hypertrophic scars (HS) often bother
patients because of their unsightliness, pain, itching, and hindrance to movement. There are no
decisive treatments or prevention methods for keloid scarsand HS, which worry patients and their
parents (1). There have been studies conducted
on postoperative keloid and HS formation (2, 3),
but there are no reports on this formation after
surgery for congenital cardiac conditions, in
which cyanosisis often presento
We have designed this study, therefore, to analyze fue factors afIecting keloid and HS development after congenital cardiac surgery. We algo
evaluated the preventive effect of tranilast, which
inhibits the collagen synthesisof keloid fibroblasts
(4).
StudyDesign: Postoperative scars were studied in 75
patients 3 months alter congenital cardiac surgery by
median skin incision. The mean ageof fue 51 males and
24 females was 2.7 :t 2.3 years (range,2 days-12years).
1rhe scars were evaluated according to degree of redness, expressed as redness score, and skin blood flow,
as measured by laser Doppler imaging. Skin blood flow
ratio was calculated asblood flow at fue scar divided by
blood flow below fue navel. Mter surgery, 40 patients
received 5 mg/kg/ dar of tranilast, which inhibits fue
collagen synthesis of keloid fibroblasts.
Results:None of fue 75 patients had keloid fonnation
and 21 (28%) developed HS alter operation. Mean age
of patients with HS (HS (+) group) was4.4 :t 3.3 years
and that of patients with no HS development (HS (-)
group) was 1.5 :t 1.9 years (p < 0.01). There were no
significant differences between fuese two groups in
gender or in pre- or postoperative cyanosis.Hypertrophic scar (+) patients exhibited significantIy higher
skin blood flow ratios than HS (-) patients (2.7 :t 1.3
versus 1.4 :t 0.6; P < 0.001). Hypertrophic scar was
seen in 11 of 40 tranilast administered patients (28%)
and in 10 of 34 patients not receiving tranilast (29%)
(NS). Hypertrophic scar was less apparent in fue patients who received tranilast versus those who did not;
redness scores were 29.5 :t 16.5 and 51.6 :t 14.9,
respectively (p < 0.01).
Methods
Conclusions:
These data suggestthat age and skin blood
flow ratio were fue factors affecting HS develop~ent.
Postoperative use of tranilast did not affect fue frequency of HS development but did reduce its redness.
,.'
Received October 11, 1996; Revised April 24, 1997; Accepted April
29,1997.
From the Department ofCardiovascular Surgery,OkayamaUniversity
Medical School, Okayama,]apan.
Correspondence address: Koki Nakamura, Department of Cardiovascular Surgery, Okayama University Medical School,2-5-1Shikata-cho,
Okayama 700,]apan.
@ 1997 by the American College of Surgeons
Publishedby ElsevierSciencéInc.
@ 1997 by the
Seventy-fivechildren who underwent cardiac surgery by median skin incisions were studied prospectively: ages ranged from 2 days to 12 years
(mean of2.7:!: 2.3 years). There were 51 boys and
24 girls. Patients were excluded from this study
based on fue following criteria: reoperation on
previous operation scars, wound infection, and
treatment with steroid or antiallergic drugs. Diagnoses are presented in Table 1. Surgical procedures included 67 total corrections and 8 palliations. Thirty-four patients (45%) had preoperative
and 9 (12%) had postoperative cyanosis.
AlI parents of patients were informed about fue
prophylactic use of tranilast. For 3 months after
fue operation, 5 mg/kg/ dar of sweetened, powdered tranilast (Kissei Pharmaceutical Co, Ltd,
Nagano,]apan) was given orally topatients whose
families had consented. The parameters of fue
group receiving tranilast (tranilast (+) group)
were very similar to those ofthe group that did not
(tranilast (-) group) (Table 2).
The same technique was used to clase the sterISSN 1072-7515/97/$17.00
218
220
AM COLL SURG SEPTEMBER1997
VOLUME185:218-223
B
A
FIc 1. Keloid and hypertrophic scarsamples. (A) Photographic sample of a keloid scar; no keloid wasobserved in our study.
(B) Hypertrophic scar.
7.9% in the H-S (+) and 88.4 :!: 12.9% in the HS
(-) group (NS). Postoperative SaO2 was 96.6 :!:
Hypertrophic scarswere observed in 21 of 75 pa- 2.9% and 94.8 :!: 6.0% in the respective groups
tients (28%) and keloids were not present 3
(NS; Table 3). Preoperative total protein and almonths after surgery (Fig. lA, B). Scarrednesswas bumin were significantly higher in the HS (+)
seen in 49 patients (65%). Patients were divided
group as was total protein measured 3 months
into two groups: HS (+) group (n = 21) and HS
postoperatively (Table 3).
(-) group (n = 54).
Forty patients (29 boys and 11 girls) received
Mean patient age at the time of the operation
tranilast (tranilast (+) group) and 34 patients (21
was 4.4 :t 3.3 years in the HS (+) and 1.5 :t 1.9 boysand 13 girls) did not (tranilast (-) group)..One
yearsold in the HS (-) group (p < 0.01; Table 3).
patient wasremoved from fue study after ceasingto
Hypertrophic scar~were seen in 2 of 35 patients
take tranilast without any particular reason. Eleven
under and 19 of 40 ayer 1 year of age. Patients
of fue 40 tranilast (+) patients (28%) and 10 of 34
older than 5 years developed HS more frequently
tranilast (-) patients (29%) developed HS (NS;
(9 of 15); neonates had none. Gender made no
.-Table
2). Among fueseHS (+) patients, fue redness
difference in HS development.
score
was
29.5 :!: 16.5 in fue former and 51.6 :!: 14.9
Cyanosiswas observed preoperatively in 34 pain
fue
latter
group (p < 0.01).
tients, ofwhom 7had HS (21 %); of9 patientswith
Skin
blood
flow ratio was 2.7 :!: 1.3 in the HS
postoperative cyanosis,1 had an HS (11%). The
(+)
group
(n
= 19) and lA :!: 0.6 in fue HS (-)
relationship between cyanosis and HS formation
group
(n
=
53)
3 months after surgery (p < 0.001;
was not statistically significant as measured by the
Table
3).
Figure
2 shows that among the patients
chi-square test. Preoperative SaO2 was 92.2 :t
Results
,
:Table
Nakamura
et al
POSTOPERATIVE HWERTROPHIC SCARS IN CHILDRE~
221
3. Group With Hypertrophic ~ars V rsus Group Without Hypertrophic Scars
HS (+) group {n = 21~
operative
data
~
..'1
Gender (male/female)
Skin blood flow ratio (1 mo after operation)
Skin blood flow r¡itio (3 mo after operation)
SaO2 (%) level
Red blood celIs (X IO6/mm3)
Hemoglobin (g/dL)
Hematocrit (%)
White blood cells (X 103/mm3)
Neutrophil (%)
Platelet (X lOs/mm3)
Total protein (mg/dL)
Albumin (mg/dL)
4.4 = 3.3t
13/8
3.0= 1.6:
2.7 = 1.3§
:92.2= 7.9
4.9 = 0.6
'13.6= lA
41.0 = 4.0
111.2=3.2
39=
17
Postoperative
data
96.6 :!: 2.9
4.5 :!: 0.4
12.6 :!: 0.8
37.5 :!: 2.2
9.0 :!: 2.4
41:!: 18t
i311= 72
342 :!: 85
7.0 = 0.7t
4A = 0.2:
4.3 :t 0.3
1
7.0 :t 0.5t
-
HS (-) group (n = 54)
Preoperative
data
1.5:t 1.9
38/16
1.5:t 0.8
1.4 :t 0.6
88.4 :t 12.9
5.0:t 0.9
14.3:t 2.4
43.2 :t 7.4
10.3 :t 3.8
35:t 15
303:t 106
6.4 :t 0.6t
4.1 :t 0.4%
Postoperative
data
j 6.0:
94.8
4.5 j
12.5 j
37.2
j
8.7 j
34 j
343 j
6.4 ~
4.2 ~
o.s:
1.6:
4.7:
2.4:
lS:
106:
O.st:
0.3
tp < 0.01. :p < 0.05.*p < 0.001.
with scar redness the skin blood flow ratio ~as
significantly higher in HS (+) than in HS (!-)
patients. Among all the patients, 27 scarshad ~lso
been observed1 month postoperatively. HS fin*lly
appeared in 8 of 27 patients although HS *as
obvious in only 3 patients 1 month after surg~ry.
Skin blood flow ratio was 3.0 ::t 1.6 in the HS (ft)
group (n = 8) and 1.5 ::t 0.8 in the HS (-) grorp
(n = 19, P < 0.05).
Discussion
Median skin incisions cross the Langer line (8,¡9)
but were not a factor affectingkeloid or HS in this
study, because all patients received the incisi~n.
Keloid and HS look similar but they were diftrrentially diagnosed according to the criteria ofPtacock and colleagues and Cohen and Peacdck
(5,6). Indeed, in some patients it mar be diffictIlt
to distinguish them, but in our patients, we w~re
able to diagnose no keloid scars. Therefore we
focused on HS in this study.
Lista and Thompson (2) reported that unsightly
scars, including HS, appeared less frequently lin
males and younger patients. In our study, youn~er
patients had HS lessfrequently, but gender ma~e
no difference.
There was a relationship between the wou*d
healing status and skin blood flow as measured ~y
laser Doppler flowmetry (10-12). Ehrlich a*d
Kelly (10) reported that skin blood flow increased
during fue early postinjury period and then qeclined to normal skin levels during the norntal
healing process. No difference between HS (+)
and HS (-) patients was observed 1 month po~toperatively in skin blood flow, but it remainfd
high beyond 90 days in the HS (+) group (10).
Our study demonstrated that skin blood flow ratio
was high in HS (+) patients even before HS had
appeared. Therefore, it might be possible to predict HS by high skin blood flow ratio 1 month after
surgery. We recommend that scars should be
treated more carefully if high skin blood flow ratio
is observed at that time. Whether the high skin
blood flow ratio is the cause or the result of HS is
unknown. There were no more changes in skin
blood flow ratio between the 1- and 3-months
postoperative measurements.
The relationship between HS and hypoxia is
unknown. It is reported that wound tissue has
7-30 mm Hg oflocal oxygen tension (13-15). Low
oxygen tension in wounds activatesfibroblasts and
synthesizesmore collagen with the production of
transforming growth factor-{31.This suggeststhat
wound hypoxia mar be the cause of HS. It also has
been reported that HS and keloids mar be resolved by hypoxia through light topical pressure
(3). In patients with congenital heart diseases,
various degrees of cyanosiswith frequent hypercythemia and increased coUateralvesselsin the skin
were observed.We had supposedthat wound healing might be disturbed and that HS would arrear
more frequently in cyanotic patients. But there
was no relationship between HS and cyanosis or
between HS and SaO2. The level of PaO2' which
was seen in cyanosis patients, might not be low
enough to affect the local oxygen tension. Oxygen
supply to wound tissue mar be sufficient, because
of compensativehypercythemia and increased collateral vesselsin the skin.
Tranilast was used originally for bronchial
1997 VOLUME185:218-223
222 J AM COLLSURG SEPTEMBER
HS (-)
redness
HS (-)
redness (+)
HS (+)
redness (+)
FIG 2. Skin blood flow ratio among 3 groups. Skin blood flow ratio in hypertrophic scar (HS) (-) and redness (-), HS (-)
and redness (+) and HS (+), and redness (+) patients were 1.2 :!: 0.6, 1.6:!: 0.7 and 2.7 :!: 1.3 respectively. *p < 0.05, **p <
0.01.
of tranilast did not de crease the incidence of HS
asthma treatment (16) and has been used to treat
formation,
but it did reduce redness in HS.
keloids and HS (17). Its proposed mechanism is the
suppression, in mast cells and inflammatory cells, of
the release of chemical mediators such as histamine
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