Pilot Studies On Healing Effect And Mechanism Of Postoperative Imiquimod 5% Cream On The Recurrence Rate Of Excised Keloids

Keloids are common benign skin tumor because of the excess reaction of the connective tissue to the trauma.The pathogenesis of it remains unclear.Surgical excision is a primary approach to treat keloids,but it is seldom used only because of the high recurrence rate.Several adjunctive therapies,most commonly postoperative triamcinolone injections,electron beam irradiation,topically applied silicone gel sheeting have been used.Historic data showed that for keloids excised and treated after surgery with these methods still remains high recurrence rate.Although there is no commonly satisfied treatment for keloids at present,the clinical and laboratorial studies of keloid are never paused.Chapter One:Clinical StudiesTreatment of Keloid with Surgery in Combination with Atopic of Imiquimod 5% CreamObjective:To search for a new approach of keloid treatment.Methods: Examined the effects of postoperative imiquimod 5%cream on the recurrence of 27 keloids excised surgically from 17 patients.Starting on the next night of surgery, imiquimod 5%cream was applied for 8 weeks or 12 weeks.Patients were examined at month 1,2,3,6,9 and 12 for local erythema,edema,erosions,pigment alteration, and recurrence of keloids.Results:Of the 27 keloids evaluated at 12 months,10 cases(37%) were cured without relapse;12 cases got partly remission;5 cases (19%) relapsed.Common side effects were erythema,edema,erosions,pigment alteration with incidences of 63%in total.No severe side effect was observed. Conclusions:Postoperative imiquimod 5%cream therapy is a safe and effective method in decreasing recurrence rate of keloid formation. The histologic hallmark of a keloid is persistend proliferation of fibroblast and excessive amounts of collagen and other extracellular matrix components.Imiquimod can prevent keloid recurrence after surgery,then it must can change the histologic hallmark of the keloid firstly.Chapter Two:Laboratorial StudiesⅠThe Effect of Imiquimod on Cell Modality,Proliferation and Collagen Production in Cultured Keloid FibroblastObjectives:To investigate the effect of imiquimod on cell modality,proliferation and collagen production in cultured KFb.Methods:Primary culture of fibroblast was established from the excised keloid from three keloid patients.Fb was cultivated with various concentrations of imiquimod for 48 hours.Inverted microscope was used to observe the morphological alteration of Fb;MTT test was used to assess cell proliferation:Hydroxyproline mensuration reagent box was used to mensurate the collagen production.Results:KFb showed visible morphological alteration under the action of 100μg/mL～200μg/mL imiquimod;Imiquimod of 75μg/mL～200μg/mL concentration can prominently inhibit the collagen production(P＜0.05);At 24h,48h,only imiquimod of 100μg/mL～200μg/mL concentration can prominently inhibit the proliferation of Fb(P＜0.05),but at 72h, 25μg/mL～200μg/mL imiquimod all can prominently inhibit the proliferation of Fb (P＜0.05).Conclusions:Imiquimod of certain concentrations can prominently inhibit the Fb proliferation and collagen production in a dose & time-dependent manner.Our previous studies showed that high level of telomerase expression may be related to the pathogenesis of the keloid.Meanwhile,there is clinical evidence proved that imiquimod can prevent the recurrence of keloid after surgery.Then,is it the approach that the imiquimod prevent the recurrence of keloid after surgery though the way of inhibiting the activity of telomerase? Chapter Three:Laboratorial StudiesⅡThe Effect of Imiquimod on Activity of Telomerase in Cultured Keloid FibroblastObjectives:To investigate the effect of imiquimod on telomerase activity of KFb.Methods:Primary cultivated KFb was cultivated with various concentrations of imiquimod for 48 hours.SS-TRAP and grayscale assay was used to measure the activity of telomerase.Results:Along with the increase of imiquimod concentrations, the activity of telomerase was decreased.Conclusions:Imiquimod of 10μg/mL～200μg/mL concentrations can prominemly inhibit the activity of telomerase in a dose-dependent manner.Conclusions of the whole studies:1,Imiquimod can effectively prevent the keloid recurrence after surgery.2,The approach that the imiquimod prevent the recurrence of keloid after surgery is through the way of inhibiting the activity of telomerase.