***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To assess the safety and efficacy of the long-pulsed pulsed dye laser ( LP PDL ) ( 595 nm ) with photodynamic therapy ( PDT ) for treatment of actinic keratoses ( AKs ) . DESIGN Prospect i ve , controlled study with 10-day and 2- , 4-,6- , and 8-month follow-ups . SETTING Clinical research center . PATIENTS Volunteer sample of 41 patients ( age range , 35 - 91 years ; skin types I-III ) with AKs . INTERVENTION Single treatment with application of topical 20 % 5-aminolevulinic acid for 3 hours or 14 to 18 hours , followed by LP PDL irradiation at 595 nm . Controls received LP PDL irradiation alone . MAIN OUTCOME MEASURES Safety assessment s , treatment and recovery times , and efficacy assessment s , including patient mean percentage of lesions cleared and distribution of patients by percentage of lesions cleared for different anatomic sites . RESULTS We observed no to slight pain ; slight to moderate erythema ; no purpura , crusting , or scarring ; treatment time of 1 lesion per second ; and resolution of erythema by 7 to 14 days . The patient mean ( 95 % confidence interval ) percentage of head lesions ( 2620 lesions ) cleared after 1 treatment was 99.47 % ( 99.44%-99.50 % ) at 10 days , 98.19 % ( 98.15%-98.23 % ) at 2 months , 92.94 % ( 92.73%-93.14 % ) at 4 months , 91.65 % ( 91.15%-92.15 % ) at 6 months , and 90.32 % ( 78.10%-100 % ) at 8 months . For extremities ( 949 lesions ) , these were 83.1 % ( 81.4%-84.9 % ) at 10 days , 75.5 % ( 73.4 - 77.6 ) at 2 months , 70.9 % ( 68.9%-72.8 % ) at 4 months , 92.0 % ( 84.0%-100 % ) at 6 months , and 100 % at 8 months . For trunk ( 53 lesions ) , these were 85 % ( 74%-100 % ) at 10 days , 85 % ( 74%-100 % ) , and 65 % ( 50%-80 % ) at 4 months . No difference in safety or efficacy was found between the 3-hour and 14- to 18-hour incubation times . In the laser-only control group , no decrease in lesions was observed . Among 31 patients with head lesions , 28 ( 90 % ) at 10 days , 19 ( 70 % ) at 2 months , 9 ( 47 % ) at 4 months , 5 ( 42 % ) at 6 months , and 5 ( 56 % ) at 8 months were completely ( 100 % ) clear following a single treatment . Skin biopsy specimens of nonresponding lesions demonstrated a high rate of squamous cell carcinoma and other non-AK neoplasms . CONCLUSIONS Treatment of AKs using LP PDL ( 595 nm ) at nonpurpuric parameters following topical application of 5-aminolevulinic acid is safe and effective . The advantages may include minimal discomfort , rapid incubation treatment and recovery times , excellent posttreatment cosmesis , high efficacy rates with respect to head lesions , and practical applicability to large body surface areas BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma . Treating actinic keratoses and the surrounding skin area ( i.e. , field therapy ) can eradicate clinical and sub clinical actinic keratoses . Topical field therapy currently requires weeks or months of treatment . We investigated the efficacy and safety of a new topical field therapy for actinic keratosis , ingenol mebutate gel ( 0.015 % for face and scalp and 0.05 % for trunk and extremities ) . METHODS In four multicenter , r and omized , double-blind studies , we r and omly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo ( vehicle ) , self-applied to a 25-cm(2 ) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities . Complete clearance ( primary outcome ) was assessed at 57 days , and local reactions were quantitatively measured . RESULTS In a pooled analysis of the two trials involving the face and scalp , the rate of complete clearance was higher with ingenol mebutate than with placebo ( 42.2 % vs. 3.7 % , P<0.001 ) . Local reactions peaked at day 4 , with a mean maximum composite score of 9.1 on the local-skin-response scale ( which ranges from 0 to 4 for six types of reaction , yielding a composite score of 0 to 24 , with higher numbers indicating more severe reactions ) , rapidly decreased by day 8 , and continued to decrease , approaching baseline scores by day 29 . In a pooled analysis of the two trials involving the trunk and extremities , the rate of complete clearance was also higher with ingenol mebutate than with placebo ( 34.1 % vs. 4.7 % , P<0.001 ) . Local skin reactions peaked between days 3 and 8 and declined rapidly , approaching baseline by day 29 , with a mean maximum score of 6.8 . Adverse events were generally mild to moderate in intensity and resolved without sequelae . CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses . ( Funded by LEO Pharma ; Clinical Trials.gov numbers , NCT00742391 , NCT00916006 , NCT00915551 , and NCT00942604 . ) BACKGROUND Actinic keratoses ( AKs ) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma ( SCC ) . Treatment at an early stage may prevent development of SCC . Current treatment options are highly destructive and associated with significant side-effects . Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis . Previous studies have demonstrated that 3 % diclofenac in 2.5 % hyaluronan gel is effective and well tolerated in the treatment of AK . The present study was design ed to further explore the therapeutic potential of this gel . METHODS This r and omized , double-blind , placebo-controlled trial involved out patients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2 ) blocks . Patients received either active treatment ( 3 % diclofenac gel in 2.5 % hyaluronan gel ) or inactive gel vehicle ( hyaluronan ) as placebo ( 0.5 g b.i.d . in each 5 cm(2 ) treatment area for 90 days ) . Assessment s included the Target Lesion Number Score ( TLNS ) , Cumulative Lesion Number Score ( CLNS ) , and Global Improvement Indices rated separately by both the investigator ( IGII ) and patient ( PGII ) . RESULTS Results obtained from 96 patients at follow up ( 30 days after end of treatment ) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group ( 50 % vs. 20 % ; P < 0.001 ) . There was also a significant difference between the two groups in CLNS , with 47 % of patients in the active treatment group having a CLNS = 0 compared with only 19 % in the placebo group ( P < 0.001 ) . The proportion of patients with an IGII score of 4 ( completely improved ) at follow-up was 47 % in the active treatment group compared with only 19 % in the placebo group ( P < 0.001 ) ; for PGII these values were 41 % vs. 17 % , P < 0.001 . Both treatments were well tolerated , with most adverse events related to the skin . CONCLUSIONS Topical 3 % diclofenac in 2.5 % hyaluronan gel was effective and well tolerated for the treatment of AK Background Although photodynamic therapy ( PDT ) is becoming an important treatment method for skin lesions such as actinic keratosis ( AK ) and superficial basal cell carcinoma , there are still discussion s about which fluence rate and light dose are preferable . Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates . However , these results have not yet been verified in humans INTRODUCTION After renal transplantation , the incidence of premalignant and malignant skin lesions is high . Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas , but treatment is hampered by frequent side effects . No optimal long-term dosing advice is available . METHODS A total of 26 long-term renal transplant recipients were r and omized to 1-year treatment with acitretin  , either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months . At 9 different time points , the number of actinic keratoses and tumors was counted , and erythema and thickness of the lesions , and severity of side effects were scored . Patient 's judgment was recorded using visual analog scores . RESULTS In both groups , the number of actinic keratoses decreased by nearly 50 % , but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study . Thickness of the keratoses decreased significantly in both groups . Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects , such as cheilitis , excessive peeling of the skin , and hair disorders . In the 14 patients r and omized to continuous treatment with a dose of 0.4 mg/kg/d , this dose could be maintained in 3 of 14 patients only . Temporary interruption of acitretin therapy was necessary in 7 of 26 patients . Patients ' contentment about the aspect of their skin increased significantly , with no differences between groups . CONCLUSIONS Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions . However , the incidence of new skin malignancies remained unchanged . Despite the high incidence of mucocutaneous side effects , patient 's contentment with the aspect of their skin increased significantly BACKGROUND There is no completely satisfactory treatment for  multiple actinic keratoses ( AKs ) .  OBJECTIVE To evaluate the efficacy of short incubation , broad-area application of delta-aminolevulinic acid followed by exposure to activating light-photodynamic therapy ( delta-ALA/PDT ) for treatment of AKs and background photodamage . The benefit of pretreatment with 40 % urea cream to enhance penetration and the use of topical 3 % lidocaine hydrochloride to decrease discomfort were also evaluated . METHODS Eighteen patients with at least 4 nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage were enrolled in the study . For 7 days , 40 % urea cream or vehicle was applied to half of the treatment area , and then delta-ALA was applied to the entire area for 1 , 2 , or 3 hours . Lidocaine hydrochloride ( 3 % ) or vehicle cream was also applied to the entire area 45 minutes before exposure to 10 J/cm(2 ) of blue light . Pain , phototoxic reactions , AK counts , and photodamage improvement were evaluated 1 day , 1 week , and 1 month after treatment in all patients and after 5 months in 10 patients . RESULTS All patients experienced mild to moderate discomfort during treatment and moderate phototoxic effects for 1 week . At 1 and 5 months there was significant reduction in AKs in all groups and significant improvement of several photodamage parameters . Different delta-ALA application times and pretreatment with urea cream or lidocaine had no significant effect on the results . CONCLUSIONS This delta-ALA/PDT protocol is safe and effective for AK treatment as well as for improving photodamage . Further studies with a larger cohort , longer follow-up , and histologic confirmation of the clinical data would be of value BACKGROUND A new 0.5 % fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available . OBJECTIVE This was a comparison of the tolerability and efficacy of the 0.5 % and 5 % fluorouracil creams in the treatment of actinic keratosis ( AK ) . METHODS During this single-blind , r and omized study , patients with > or = 6 AK lesions were treated for 4 weeks with the 0.5 % ( once daily ) and 5 % ( twice daily ) fluorouracil creams applied to opposite sides of the face . After the end of treatment , patients were 
    Output:
    
We found no data on the possible reduction of squamous cell carcinoma .
Based on investigator and participant evaluation , imiquimod treatment and photodynamic therapy result ed in better cosmetic outcomes than cryotherapy and 5-fluorouracil .
AUTHORS ' CONCLUSIONS For individual lesions , photodynamic therapy appears more effective and has a better cosmetic outcome than cryotherapy .
For field-directed treatments , diclofenac , 5-fluorouracil , imiquimod , and ingenol mebutate had similar efficacy , but their associated adverse events and cosmetic outcomes are different .