Infantile Hemangiomas. Infantile Hemangiomas

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1 The newest devices and techniques for vascular lesion treatment Kristen M. Kelly, M.D. Department of Dermatology Disclosures: Off-label uses will be discussed Drug donated for research: Light Sciences Oncology, Novartis Light Sources donated for research or to clinic: Light Sciences Oncology; Candela-Syneron Advisory Consultant: Experion; Munda Pharma Research Supported by ASLMS; NIH, Sturge-Weber Foundation Vascular tumors Rapid growth followed by stabilization and involution Observation Steroids Topical; Intralesional; Systemic 2-3 mg/kg Propranolol/Timolol/Other Beta blockers Ulceration Management: Barrier creams; Propranolol/Timolol; PDL Laser Surgery Propranolol was effective at a dose of up to 3 mg/kg/day for 6 months in treatment of infantile hemangioma Multicenter, randomized, double-blind phase 2-3 trial funded by Pierre Fabre of a pediatric specific oral solution 460 infants randomly assigned to placebo or 1 or 3 mg/kg/d for 3 or 6 months with a pre planned interim analysis; final assessment week 24; 3 mg/kg for 6 months for final analysis 88% showed improvement by week 5 (5% of placebo) Complete or near complete resolution 60% (placebo 4%) 10% required systemic retreatment Hypoglycemia, hypotension, bradycardia and bronchospasm occurred infrequently with no significant placebo difference Leaute-Labreze C, Hoeger P et al. A randomized controlled tiral of oral propraolol in infantile hemangioma. N Engl J Med, 2015 Feb; 372(8): Leaute-Labreze C, Hoeger P et al. A randomized controlled trial of oral propranolol in infantile hemangioma. N Engl J Med, 2015 Feb; 372(8): When to use laser for infantile hemangiomas Patients who are not beta blocker candidates - rare Good adjunct when there is a superficial component Can achieve more complete removal Can decrease needed time for beta blocker Recurrence as beta blocker is tapered or stopped Residua left after active treatment Vascular targeting lasers for any residual redness Ablative fractional laser for any textural change Goal of early treatment is to avoid any residua In my opinion/experience IH 1) Infantile hemangiomas: PDL is best laser option; lower energies especially during the proliferative stage; may increase once stabilized or involuting 2) Combination of PDL and propranolol excellent option for lesions with a deep component, ulcerated or rapidly progressing 3) Combination of PDL and timolol is another option for thin lesions 4) Starting treatment early can avoid need for reconstructive treatments later 1

2 Port Wine Stain Birthmarks Vascular Malformation Slow progression (tissue thickening, nodules) over decades Lasers; Light Sources Adjunctive Treatment Start Treatment Early Increase blood flow to the PWS area by: Placing the patient in Trendelenberg How can I improve treatment effect? PDL Treatment Parameters PWS Treatment 585 or 595 nm Wavelength ms pulse duration Vary pulse duration and wavelength over time to achieve optimal results Larger spot size when possible 6-13 J/cm 2 ; Use 7mm spot size for higher energies (if needed) Consider multiple passes in single treatment session Consider varying wavelengths and devices Watch skin carefully during treatment Know desired endpoint In my opinion/experience PWS Treatments repeated at 4 week intervals for facial lesions in lighter skin types (shorter intervals may improve outcome) Longer intervals between treatments for extremity lesions and if there is significant hyperpigmentation Multiple treatments are required (3-15 or more)! 1) Port wine stain birthmarks: higher energies and more treatments required (partly because lesion does not involute by itself and in fact recurrence of blood vessels occurs) 2) Start as early as possible 3) Alternative treatments needed Destructive methods in combination with anti-angiogenic agents Studies needed to evaluate adjunctive options in children 2

3 Rapamycin + PDL 23 patients with SWS and facial PWS Placebo; PDL + Placebo; 1% Rapamycin alone; PDL + Rapamycin Analysis at 6, 12, and 18 weeks after intervention PDL+Rapamycin yielded the lowest digital photographic image score (greatest improvement) and lowest percentage of blood vessels on histologic analysis Well tolerated; rapamycin was detected in the blood Topical rapamycin combined with PDL in the treatment of capillary vascular malformations in SWS: Phase II, randomized double-blind, intraindividual placebo controlled clinical trial JAAD : Photographs taken before treatment (A), after 6 weeks (B), and after 12 weeks (C); posterior control at 18 weeks (D). The lateral part of port-wine stain was treated with laser, and in this patient, according to the randomization, the rapamycin treatment was applied in the superior half. Note an important clinical subjective improvement in OV1 (B) and in OV2 (C) in the part treated with rapamycin 1 laser, and less improvement in the part treated with laser alone. This improvement in the rapamycin 1 laser part seems to persist in time from OV2 (C) until OV3 (D). The other 2 parts did not demonstrate improvement. New Device in Development 3 technologies: Pulsed dye + Nd:YAG + RF Theoretical Modeling More powerful PDL with extended dye life PDL alone RF alone PDL+RF 2 Zoom handpieces & delivery system options: one for each cooling option. 2 Cooling options: DCD or EverCool, contact cooling. 5 + Treatment Modes depending on technologies & cooling options. Vessel Dia.(µm) Depth(mm) tr (ms) A B C D E At end of RF pulse, benefit of PDL+RF is obvious. Vessels temperatures persist leading to more thermal damage. Associated with Tuberous Sclerosis Slow progression; fairly rapid recurrence Lasers; Light Sources Rapamycin: topical and/or oral Angiofibromas Pulsed-dye laser treatment 10 mm; 1.5 ms; 7.5 J/cm 2 ; 30 ms cooling Ablative fractional resurfacing 15 mm; 70 mj; 40% Pinpoint electrosurgery to papular fibrotic lesions 0.2% topical rapamycin ointment bid Tuberous Sclerosis Bae-Harboe YS, Geronemus RG. Targeted topical and combination laser surgery for the treatment of angiofibromas. Lasers Surg Med. 2013;45:

4 How can I make treatment easier for pediatric patients? Child life specialists assist us with management of pediatric patients when general anesthesia used 1. Laser all ready to go before child enters room 2. All adults with goggles before child enters room 3. Child brought into the room and immediately swaddled 4. Laser aid eye pads with overlying gauze 5. One staff member responsible only for eye protection 6. One staff member for holding child 7. 1 parent may be in the room but not participating in the procedure General Anesthesia Mask inhalation anesthesia performed by experienced pediatric anesthesiologists Common intraoperative pain meds administered 1) Intranasal fentanyl (also "smooths" wake up in addition to pain management) 2) Rectal acetaminophen No NSAIDS when treating vasculature due to clotting inhibition These meds can be given without an i.v. after patient is asleep The families of pain meds work synergistically FDA Drug Safety Communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women 12/14/2016 The U.S. Food and Drug Administration (FDA) is warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children s brains. Consistent with animal studies, recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning. However, further research is needed to fully characterize how early life anesthetic exposure affects children s brain development. To better inform the public about this potential risk, we are requiring warnings to be added to the labels of general anesthetic and sedation drugs (see List of General Anesthetic and Sedation Drugs Affected by this Label Change). We will continue to monitor the use of these drugs in children and pregnant women and will update the public if additional information becomes available. Anesthetic and sedation drugs are necessary for infants, children, and pregnant women who require surgery or other painful and stressful procedures, especially when they face life-threatening conditions requiring surgery that should not be delayed. In addition, untreated pain can be harmful to children and their developing nervous systems. Health care professionals should balance the benefits of appropriate anesthesia in young children and pregnant women against the potential risks, especially for procedures that may last longer than 3 hours or if multiple procedures are required in children under 3 years. Discuss with parents, caregivers, and pregnant women the benefits, risks, and appropriate timing of surgery or procedures requiring anesthetic and sedation drugs. Parents and caregivers should discuss with their child s health care professional the potential adverse effects of anesthesia on brain development, as well as the appropriate timing of procedures that can be delayed without jeopardizing their child s health. GAS Study: General Anesthesia compared to Spinal anesthesia International, randomized controlled trial conducted at 28 hospitals - 7 countries - February 2007-January children less than 6 months old; hernia repair randomly assigned to awake-regional anesthesia or sevoflurane-based general anesthesia General anesthesia group - an average of 54 minutes Two-year outcome data available for 532 children Mean cognitive composite score was 98.6 for awake regional and 98.2 for general anesthesia not statistically different Primary outcome of the GAS Study will be performance on a test of intelligence at age 5 Davidson AJ, Disma N et al. Neurodevelopmental outcomes at 2 years of age after general anesthesia and awake-regional anesthesia in infancy: an international multi-centre randomised controlled trial. Lancet Jan; 387; Association between a single general anesthesia exposure and neurocognitive outcomes 105 sibling pairs, exposed siblings and unexposed sibling had IQ testing at mean ages 10.6 and 10.9 years Exposed children received inhaled anesthetic agents from minutes with a median duration of 80 minutes Mean IQ scores were not statistically significantly different: Exposed sibling: full=111; performance = 108; verbal= 111 Non-exposed sibling: full=111; performance = 107; verbal= 111 No diffrences in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language or behavior Further study for repeated and prolonged exposure and vulnerable subgroups Davidson AJ, Sun LS, Guohua L, Miller TL et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA. 2016; 315(21):

5 Association between a single general anesthesia exposure and neurocognitive outcomes 33 patients Average age at time of first treatment 1.9 years; Average number of treatments before the age of 4 years was 6.7 Average age at time of survey 7.8 years Anesthetics included nitrous oxide, isoflurane and IV propofol ADHD 3%; Axiety 6.1%; behavioral disorder 3.0%; language disorder 3.0%; speech disorder 3.0%; motor disorder 6.1% Rates are similar to those in the US population Study is small but no increased risks when comparing with prevalence rates reported in the literature Terushkin V, Brauer J, Bernstein I Geronemus R. Effect of General Anesthesia on Neurodevelopmental abnormalities in Children Undergoing Treatment of Vascular Anomalies with Laser Surgery. A retrospective Review. Derm Surg Summary for Pediatric Laser Treatments Lasers can be used safely in children For some conditions - results are improved when treatment performed in children Standard laser safety procedures such as eye protection must be followed Some special consideration should be taken when treating children Considering potential fear Discussing and considering options for anesthesia Colleagues: Bernard Choi Residents and Post-Doctoral Students: Sean White Wes Moy Jonathan Yao Bruce Yang Brent Martin Acknowledgements Funding Sources: Sturge Weber Foundation American Society for Laser Medicine and Surgery National Institutes of Health (HD065536) The project described was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. 5