Rafael A. Couto

Infantile hemangioma: clinical assessment of the involuting phase and implications for management.

Background: Infantile hemangioma involutes during childhood; the tumor decreases in size and its color fades. Reconstructive procedures are often withheld until the lesion stops improving. The purpose of this study was to determine the age at which involution of infantile hemangioma ends, and factors that influence its regression. Methods: Consecutive patients with infantile hemangioma managed between 2007 and 2011 were studied retrospectively. The outcome variable was age at which the appearance of the infantile hemangioma ceased to improve. Predictive variables were sex, lesion size, location, tumor depth, ulceration, and history of treatment (local or systemic corticosteroid). Results: The study comprised 81 patients. Infantile hemangioma was located on the head/neck (79.0 percent), trunk (13.6 percent), or extremity (7.4 percent). Average tumor area was 9.3 ± 9.7 cm2. Twenty-six percent of the cohort was treated with a corticosteroid during the proliferative phase and 87.6 percent underwent reconstruction for a residual deformity. Kaplan-Meier analysis estimated that involution ceased at a median age of 36 months (interquartile range, 30 to 42 months), and 92 percent of tumors completed involution by 48 months. Multivariate Cox proportional hazards regression model showed that sex (p = 0.80), lesion size (p = 0.09), location (p = 0.77), tumor depth (p = 0.74), ulceration (p = 0.18), and previous local (p = 0.73) or systemic (p = 0.60) corticosteroid treatment did not influence regression. Conclusions: Most infantile hemangiomas do not improve significantly after 3.5 years of age. Reconstructive procedures should be considered at this age; the tumor has been allowed to regress and the deformity is improved before the development of long-term memory and psychosocial morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Oral prednisolone for infantile hemangioma: efficacy and safety using a standardized treatment protocol.

Background: The efficacy of oral corticosteroid therapy for problematic infantile hemangioma depends on dosage, duration of treatment, and definition of therapeutic response. The purpose of this study was to determine the efficacy and safety of oral corticosteroid therapy using a standardized treatment protocol. Methods: The study comprised 25 consecutive patients with infantile hemangioma managed with oral prednisolone between 2007 and 2010. All patients were given 3 mg/kg/day for 1 month, followed by a 0.5-ml taper every 2 to 4 weeks. Predictive variables were age at initiation of treatment, sex, location, lesion size, and tumor depth. Treatment response was defined as no response, stabilization, or regression. Rebound growth and drug morbidity were recorded. Results: Tumors primarily affected the cheek (n = 12), orbit (n = 8), nose (n = 2), forehead (n = 2), or neck (n = 1). Treatment was initiated at an average age of 12.1 ± 7.2 weeks for 32.2 ± 10.0 weeks. All tumors responded to therapy; 88.0 percent (n = 22) regressed and 12.0 percent (n = 3) stabilized. Age at initiation of treatment, sex, location, lesion size, and tumor depth did not affect treatment response (p = 0.13). Rebound growth occurred in 8.0 percent of infants, and 20.0 percent demonstrated a transient cushingoid appearance. No patients suffered drug morbidity. Conclusions: The administration of oral prednisolone using a standardized protocol of 3 mg/kg given once daily for 1 month, followed by a taper until the infant is 10 months of age, is an effective treatment for infantile hemangioma. Therapy is safe because it is limited to several months and the dosage is continually weaned as the infant gains weight. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Management of Primary and Secondary Lymphedema: Analysis of 225 Referrals to a Center.

BackgroundLymphedema is the chronic, progressive enlargement of tissue due to inadequate lymphatic function. Although lymphedema is a specific condition, patients with a large extremity are often labeled as having “lymphedema,” regardless of the underlying cause. The purpose of this study was to characterize referrals to a center to determine if lymphedema should be managed by specialists. MethodsPatients treated in our Lymphedema Program between 2009 and 2013 were reviewed. Diagnosis was determined based on history, physical examination, photographs, and imaging studies. Lymphedema type (primary or secondary), location of swelling, patient age, sex, and previous management were documented. The accuracy of referral diagnosis and the geographic origin of the patients also were analyzed. ResultsTwo hundred twenty-five patients were referred with a diagnosis of “lymphedema”; 71% were women and 29% were children. Lymphedema was confirmed in 75% of the cohort: primary (49%) and secondary (51%). Twenty-five percent of patients labeled with “lymphedema” had another condition. Before referral 34% of patients with lymphedema received tests that are nondiagnostic for the disease, and 8% were given a diuretic which does not improve the condition. One third of patients resided outside our local referral area. The average time between onset of lymphedema and referral to our Lymphedema Program was 7.7 years (range, 1–59 years). ConclusionsPatients presenting to a center with “lymphedema” often have another condition, and may be suboptimally managed before their referral. Patients with suspected lymphedema should be referred to specialists focused on this disease.

Cranial particulate bone graft ossifies calvarial defects by osteogenesis.

Background: Cranial particulate bone graft heals inlay calvarial defects and can be harvested as early as infancy. The purpose of this study was to test the hypothesis that particulate bone promotes ossification primarily by osteogenesis. Methods: Freshly harvested particulate bone, devitalized particulate bone, and high-speed drilled bone dust from rabbit calvaria were assayed for metabolic activity (resazurin) and viable osteoblasts (alkaline phosphatase). A rabbit cranial defect model was used to test the effect of devitalizing particulate bone on in vivo ossification. A parietal critical-size defect was created and managed in three ways: (1) no implant (n = 6); (2) particulate bone implant (n = 6); and (3) devitalized particulate bone implant (n = 6). Micro–computed tomographic scanning was used to measure ossification 16 weeks later; histology also was studied. Results: Particulate bone contained more viable cells (0.94 percent transmittance per milligram) compared with devitalized particulate bone (0.007 percent) or bone dust (0.21 percent) (p = 0.01). Particulate bone had greater alkaline phosphatase activity (0.13 &mgr;U/&mgr;g) than devitalized particulate bone (0.000) or bone dust (0.06) (p = 0.01). Critical-size defects treated with particulate bone had more ossification (99.7 percent) compared with devitalized particulate bone implants (42.2 percent) (p = 0.01); no difference was found between devitalized particulate bone and the control (40.8 percent) (p = 0.9). Conclusions: Particulate bone graft contains living cells, including osteoblasts, that are required to heal critical-size cranial defects. These data support the hypothesis that particulate bone promotes ossification primarily by osteogenesis.

Experimental Comparison of Cranial Particulate Bone Graft, rhBMP-2, and Split Cranial Bone Graft for Inlay Cranioplasty.

Background Particulate bone graft and recombinant human bone morphogenetic protein-2 (rhBMP-2) are options for inlay cranioplasty in children who have not developed a diploic space. The purpose of this study was to determine whether particulate bone graft or rhBMP-2 has superior efficacy for inlay cranioplasty and to compare these substances to split cranial bone. Methods A 17 mm × 17 mm critical-sized defect was made in the parietal bones of 22 rabbits and managed in four ways: Group I (no implant; n=5), Group II (particulate bone graft; n=5), Group III (rhBMP-2; n=7), and Group IV (split cranial bone graft; n=5). Animals underwent microcomputed tomography and histologic analysis 16 weeks after cranioplasty. Results Defects without an implant (Group I) demonstrated inferior ossification (41.4%; interquartile range [IQR], 28.9% to 42.5%) compared to those treated with particulate bone graft (Group II: 99.5%; IQR, 97.8% to 100%), rhBMP-2 (Group III: 99.6%; IQR, 99.5% to 100%), or split cranial bone (Group IV: 100%) (P < .0001). There was no difference between Groups II, III, and IV (P = .1). Defects treated with rhBMP-2 exhibited thinner bone (0.90 mm; IQR, 0.64 to 0.98) than particulate bone graft (1.95 mm; IQR, 1.09 to 2.83) or split cranial bone (1.72 mm; IQR, 1.54 to 1.88) (P = .006); particulate and split cranial bone grafted defects had a similar thicknesses (P = .6). Conclusions Particulate bone graft, rhBMP-2, and split cranial bone close inlay calvarial defect areas equally, although the thickness of bone healed with rhBMP-2 is inferior. Clinically, particulate bone graft or split cranial bone graft may be superior to rhBMP-2 for inlay cranioplasty.

Reharvested cranial particulate bone graft ossifies inlay calvarial defects.

Abstract Particulate bone graft (PBG) heals calvarial critical-size defects and is procured from the cranium with a hand-driven bit and brace. The donor sites ossify, and thus PBG potentially could be reharvested from the original areas. The purpose of this study was to determine if PBG obtained from a healed donor site is effective for inlay cranioplasty. A 17 × 17-mm critical-size defect was created in the parietal bones of 8 rabbits and treated with either no implant (group 1) or PBG harvested from the frontal bone (group 2). In 4 animals (group 3), a parietal defect was not created initially; PBG was harvested from the frontal bone and then discarded. Sixteen weeks later after the PBG donor sites had healed, a 17 × 17-mm parietal defect was made and filled with PBG reharvested from the previous donor area. Animals underwent micro–computed tomography 16 weeks after inlay cranioplasty. Critical-size defects in controls (group 1) exhibited partial ossification (35.1% ± 10.5%) compared with those treated with PBG (group 2) (99.1% ± 1.5%) or reharvested PBG (group 3) (99.3% ± 1.5%) (P = 0.02). No difference was found between groups 2 and 3 (P = 0.69). Bony thickness was similar in defects implanted with PBG (1.8 mm ± 1.1 mm) or reharvested PBG (2.1 mm ± 0.5 mm) (P = 0.68). Particulate bone graft reharvested from healed donor sites ossifies inlay cranial defects. Because the donor area for PBG is of partial thickness and less than critical size, reparative osteogenesis theoretically allows an unlimited supply of autologous bone for inlay cranioplasty using PBG.

Critical-Size Defect Ossification: Effect of Leporid Age in a Cranioplasty Model

AbstractThe ability of the human cranium to ossify full-thickness defects depends on the size of the area and the age of the patient. An adult leporid cranioplasty model is commonly used to study inlay cranioplasty materials; the influence of age on ossification is unknown in this model. The purpose of this study was to determine the effect of age on healing of a rabbit critical-size defect.Nineteen rabbits were divided into 4 groups: group 1 (n = 5) aged 4 months, group 2 (n = 4) aged 8 months, group 3 (n = 5) aged 12 months, and group 4 (n = 5) aged 16 months. A 17 × 17-mm defect was created in the parietal bones with preservation of the underlying dura. Animals underwent micro–computed tomography 4 months postoperatively to determine ossification of the defect.Group 1 defects healed by 28.5% (SD, 12.5%), group 2 defects ossified by 37.2% (SD, 5.7%), group 3 defects closed by 28.2% (SD, 11.9%), and group 4 defects healed by 39.4% (SD, 11.0%). No difference in ossification was found between groups (P = 0.31).Leporids as young as 4 months do not close a 17 × 17-mm defect; ossification is similar to animals as old as 16 months. Rabbits 4 months or older are suitable for a calvarial critical-size defect model.

Facial infiltrating lipomatosis: expression of angiogenic and vasculogenic factors.

AbstractFacial infiltrating lipomatosis causes diffuse overgrowth of subcutaneous fat, muscle, and bone. Because adipose tissue mass is angiogenesis dependent, the purpose of this study was to determine whether neovascularization is upregulated in this disease.Infiltrating lipomatosis tissue was collected prospectively from the preauricular cheek of 5 patients; neovascularization was compared to normal postauricular adipose. Specimens were analyzed using immunofluorescence for CD31 (microvascular density), &agr;-smooth muscle actin (pericyte marker), CD31/Ki67 (proliferating endothelial cells), and CD34/CD133 (endothelial progenitor cells). Quantitative reverse transcription–polymerase chain reaction was used to determine messenger RNA expression of progenitor cells (CD133) and factors that recruit them: vascular endothelial growth factor (VEGF-A), hypoxia-inducible factor 1&agr;, matrix metalloproteinase 9 (MMP-9), and stromal cell–derived factor 1&agr;. Angiopoietin 1 and 2, MMP-2, VEGF receptors, and neuropilin receptors were quantified using quantitative reverse transcription polymerase chain reaction.There was no difference in microvascular density, pericytic density, or endothelial proliferation between infiltrating lipomatosis and normal adipose tissue (P = 0.2). Expressions of VEGF-A, hypoxia-inducible factor 1&agr;, stromal cell–derived factor 1&agr;, angiopoietin 1 and 2, MMP-2 and -9, VEGF receptors 1 and 2, neuropilin receptors 1 and 2, and CD133 messenger RNA were not elevated compared to control fat (P = 0.1). Endothelial progenitor cells were not present in specimens of infiltrating lipomatosis.Infiltrating lipomatosis does not exhibit elevated angiogenic or vasculogenic factors compared to normal fat; the vasculature is stable. Neovascularization does not seem to play a role in the pathogenesis of this condition.

Adipofascial Flap in the Recipient Incision Site for Coverage of Vascular Pedicle in Free Tissue Transfer.

Summary: The recipient incision adipofascial flap offers a simple approach to address a tight skin closure over a vascular pedicle. This technique is not just fast and easy to perform but also adds little to no morbidity, removing a potential source of flap failure.

Apparent Age is a Reliable Assessment Tool in 20 Facelift Patients.

Background: Although the literature is replete with favorable facelift results, there are few validated facial rejuvenation outcome measures. Apparent age (AA), a visual estimate of age by objective observers, has been utilized in several studies; although attractive, AA lacks validation. Objective: The aim of this study is to examine the reliability of AA, highlighting the importance of the exclusive use of validated outcome measures in future studies. Methods: Ten blinded reviewers assessed pre‐ and postoperative photographs of 32 patients who underwent facelift. Each reviewer completed 3 surveys at 3‐month intervals composed of 40 randomly ordered photos; totaling 1200 photographs assigned an AA. The intra‐class correlation coefficient was classified as “excellent,” “good,” “fair,” or “poor.” The accuracy of assigned AA, agreement within 5 years, and reduction in AA were also evaluated. Results: The mean difference of preoperative true age from assigned AA was 2.74 ± 4.36 years. Forty‐three percent of raters were within 5‐years (±2.5) of the mean. Intra‐rater reliability preoperatively and postoperatively were 0.77 (95% CI, 0.82‐0.72) and 0.75 (95% CI, 0.79‐0.71), respectively. Inter‐rater reliability preoperatively was 0.98 (95% CI, 0.99‐0.96), while postoperatively was 0.95 (95% CI, 0.99‐0.95). Mean AA reduction was 5.23 ± 2.81, with an intra‐rater reliability 0.15 (95% CI, 0.03‐0.34) and inter‐rater reliability 0.65 (95% CI, 0.84‐0.38). Conclusion: Using current statistical measures and analysis, AA is an acceptable tool for pre‐ and postoperative facial evaluation when assessed by a group of 10 reviewers. Therefore, apparent age represents a reliable and valid objective observer assigned measure for evaluation of facelift outcomes.