Manuskiatti 2002.

Study characteristics
Methods	Study design: prospective, intra‐individual (split‐scar), randomised controlled trial conducted in the USA. Scar segment as the unit of randomisation Duration of the study: not reported Follow‐up time: 32 weeks (intermediate‐term follow‐up) Protocol was published before recruitment of participants: not reported Details of trial registration: not reported Funding sources: none reported
Participants	Number of participants assigned: 10 participants (keloidal or hypertrophic median sternotomy scars of 10 participants were divided into 5 segments, with a total of 50 segments evaluated) Segment 1 (585‐nm PDL 5J/cm²): a total of 10 segments treated (1 segment of each participant's scar) Segment 2 (TAC ‐ 20mg/mL): a total of 10 segments treated (1 segment of each participant's scar) Segment 3 (5‐FU ‐ 50mg/mL): a total of 10 segments treated (1 segment of each participant's scar) Segment 4 (TAC ‐ 1mg/mL plus 5‐FU ‐ 45mg/mL): a total of 10 segments treated (1 segment of each participant's scar) Segment 5 (no treatment ‐ control segment): a total of 10 segments not treated (1 segment of each participant's scar) Loss: none Number of participants assessed: 10 (50 segments) Segment 1: a total of 10 segments treated Segment 2: a total of 10 segments treated Segment 3: a total of 10 segments treated Segment 4: a total of 10 segments treated Segment 5: a total of 10 segments not treated Inclusion criteria: participants with previously untreated keloidal or hypertrophic median sternotomy scars at least 6 months after surgery, that were considered problematic by the participants. Exclusion criteria: not specified. Age: aged 25 to 74 years (range) Gender: female: 6; 60 (number; %); male: 4; 40 (number; %) Duration of scars (months): 7; 6 to 11.5 (mean; range) Skin phototypes: Skin type I: 1; 10 (number; %) Skin type II: 5; 50 (number; %) Skin type III: 2; 20 (number; %) Skin type VI: 2; 20 (number; %) Scar Location: median sternotomy scars Scar Length: not specified Scar Cause: post‐surgery
Interventions	Each scar was divided equally into 5 segments, with an untreated area of 1 cm between individual treated segments to avoid the global effect of PDL and intralesional formulas on the adjacent treated segments and to have a well‐defined segment for observation of each treatment modality. Five segments were randomly treated with 4 different regimens. One segment of each scar received no treatment and served as a control. The assignment of modality per segment was sequentially rotated from superior to inferior in each participant to adjust for effects of location. Segment 1: laser irradiation with a 585‐nm PDL (Photogenica V; Cyanosure Inc, Bedford, Mass) at an energy density of 5 J/cm² with a 7 mm spot without cooling for 6 treatment sessions at 4‐week intervals Segment 2: intralesional TAC (Kenalog; Westwood‐Squibb, Buffalo, NY) at a concentration of 20 mg/mL every 4 weeks for a total of 6 treatments Segment 3: intralesional 5‐FU (Roche, Nutley, NJ) at a concentration of 50 mg/mL for a total of 10 treatments (every 2 weeks for the first 8 treatments and every 4 weeks for the last 2 treatments) Segment 4: intralesional TAC (1 mg/mL) mixed with 5‐FU (45 mg/mL) for a total of 10 treatments (every 2 weeks for the first 8 treatments and every 4 weeks for the last 2 treatments) Segment 5: untreated ‐ control
Outcomes	Primary outcomes Overall Scar Improvement (Patient Self‐assessment): At the end of the study participants subjectively evaluated the improvement of their scars' severity compared with a standardised photograph taken before treatment. The results were graded as being completely clear (100% improvement) or placed in a category of 25% increments. Treatment‐related adverse effects: Almost all the participants (90%) reported mild to moderate discomfort during PDL treatment sessions. Purpuric discolorations were seen in the laser‐irradiated segments of all participants. Erosion secondary to blistering was observed in some areas treated with laser in 2 participants with skin phototype VI. Mild to moderate pain was reported by 100% of the participants, in the segments treated with TAC, 5‐FU (lasting from 30 minutes to several hours), and TAC plus 5‐FU, during injections. Spots of purpura were seen at the 5‐FU and TAC plus 5‐FU injection sites in 20% to 30% (respectively) of the participants at each follow‐up visit. One participant developed localised superficial tissue slough at the TAC plus 5‐FU injection site after the first treatment visit, but this reaction was not observed after the subsequent treatments. Treatment‐related adverse sequelae, including hypopigmentation (20%), telangiectasia (20%), and skin atrophy (10%), were seen in 50% (5/10) of the segments that received TAC injection alone. Some of these treatment‐related adverse effects were initially noted as early as week 8, and all persisted through the 32‐week follow‐up. No persistent treatment‐related adverse sequelae were observed in segments treated with the other modalities. Secondary Outcomes: Change in scar height: dial calliper (Mitutoyo Corporation, Kawasaki, Japan) was used to determine scar height by measuring the maximum vertical elevation of the scar above normal skin. Measurements were done at weeks 8, 16, 24 and 32. Change in scar erythema: scar erythema was measured using a handheld colorimeter (ChromaMeter CR‐200; Minolta, Ramsey, NJ). A higher erythema value indicates increased saturation toward red. The mean of 3 measurements obtained from each area under study was used. Measurements were done at weeks 8, 16, 24 and 32. Change in scar pliability: scar pliability was graded according to a standard scale used to assess functional mobility of the scar related to the contracture and elastic texture of the scar. Measurements were done at weeks 8, 16, 24 and 32. Change in histological findings: punch biopsy samples were obtained from 2 representative participants at week 32: 2 from the PDL‐ and TAC‐treated segments of one participant and 2 from the TAC plus 5‐FU and control segments of another participant. Each biopsy sample stained with hematoxylin‐eosin was examined for the pattern, arrangement, and characteristics of collagen bundles and fibroblasts and the vascularity features of individually treated segments.
Notes	No declaration of funding sources was available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation was cited but the method was not described.
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding of participants and personnel (performance bias) All outcomes	High risk	There is no mention about blinding of participants or health professionals. It is likely that the blinding could have been broken, and the outcomes are likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	There is no mention about the blinding of the evaluators.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants completed the study.
Selective reporting (reporting bias)	Low risk	No trial protocol is available, but all parameters listed in the methods section to assess changes in the scars were described.
Other bias	Low risk	No other sources of bias were found.