title: Long-term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: implications for effective port wine stain treatment.
abstract: OBJECTIVE
  Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.
  
  
  METHODS
  For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.
  
  
  RESULTS
  In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.
  
  
  CONCLUSIONS
  With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.
authors.affiliation: Beckman Laser Institute, University of California, Irvine, California 92617-3010, USA. wjia@uci.edu
authors.forename: Wangcun
authors.initials: W
authors.lastname: Jia
authors.forename: Victor
authors.initials: V
authors.lastname: Sun
authors.forename: Nadia
authors.initials: N
authors.lastname: Tran
authors.forename: Bernard
authors.initials: B
authors.lastname: Choi
authors.forename: Shaiw-wen
authors.initials: SW
authors.lastname: Liu
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Thuy L
authors.initials: TL
authors.lastname: Phung
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Nelson
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D003131:Combined Modality Therapy; D006224:Cricetinae; D004195:Disease Models, Animal; D053685:Laser Therapy / Q000379:methods*; D054025:Lasers, Dye / Q000627:therapeutic use*; D008297:Male; D019339:Port-Wine Stain / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D012307:Risk Factors; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020123:Sirolimus