Jonathan A. Perkins

Initiation and Use of Propranolol for Infantile Hemangioma: Report of a Consensus Conference

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Airway Management in Children with Craniofacial Anomalies

Craniofacial anomalies (CFA) predispose children to airway obstruction. A retrospective study was conducted to describe airway intervention required to manage patients with craniofacial syndromes and diseases involving the midface and mandible (i.e., Pierre Robin, Apert, Treacher Collins, Saethre-Chotzen, CHARGE, Nager, Stickler, Goldenhar, and Pfeiffer). The type of airway intervention, duration of intervention, and associated physical and medical conditions were evaluated. One hundred nine patients had charts available for review and met inclusion criteria. Sixty-five of these patients required airway management, most commonly in the first month of life, ranging from positioning to tracheotomy. Nineteen patients required a tracheotomy. Associated medical conditions and feeding difficulties were associated with airway obstruction. This study evaluates factors that predispose children with CFA to have airway problems that need treatment, as well as the types of airway management that are necessary.

Management of lymphatic malformations.

Purpose of reviewInnovative otolaryngologists, plastic surgeons, craniofacial surgeons, pediatric surgeons, radiologists, anesthesiologists, neonatologists, obstetricians, and scientists have continued to advance our understanding of the etiology, diagnosis, and treatment of lymphatic malformations. This article reviews the publications over the past 2 years with respect to these advances. Recent findingsFast-sequence MRI limits motion artifacts and allows prenatal MR to be used as a complementary study to ultrasound in the evaluation of large congenital neck masses. Three-dimensional ultrasonography may also be helpful in evaluating prenatal lymphatic malformations. Fluorescence in situ hybridization techniques can be used to evaluate lymphatic malformations for prenatal chromosomal analysis with emphasis on chromosomes 13, 18, 21, X, and Y. The sclerosing agent OK-432 is effective for macrocystic lymphatic malformations but showed less promise for microcystic lesions, mixed lesions, and lesions outside the head and neck region. Somnoplasty shows promise for reduction of tongue lymphatic malformations. Surgical excision, staged when necessary, continues to be integral to management in many cases. SummaryBasic science research has furthered understanding of lymphatic malformations. Clinical research has expanded and refined our diagnostic and therapeutic options for patients with these lesions. Further identification of genes selectively expressed by lymphatic endothelium should facilitate identification of usable vascular markers that can enable analysis of the underlying biology, physiology, pathology, and treatment of the lymphatic system and its malformations.

Lymphatic malformations: Review of current treatment:

Objective: Summarize current knowledge of lymphatic malformation medical, sclerotherapy, and surgical treatment; and highlight areas of treatment controversy and treatment difficulty that need improvement. Methods: Panel presentation of various aspects of lymphatic malformation treatment. Results: The mainstay of lymphatic malformation treatment has been surgical resection, which has been refined through lesion staging and radiographic characterization. Intralesional sclerotherapy in macrocystic lymphatic malformations is effective. Suprahyoid microcystic lymphatic malformations are more difficult to treat than macrocystic lymphatic malformations in the infrahyoid and posterior cervical regions. Bilateral suprahyoid lymphatic malformations require staged treatment to prevent complications. Lymphatic malformation treatment planning is primarily determined by the presence or possibility of functional compromise. Problematic areas include chronic lymphatic malformation inflammation, dental health maintenance, macroglossia, airway obstruction, and dental malocclusion. Conclusions: Lymphatic malformation treatment improvements have been made through radiographic characterization and staging of lymphatic malformations. Direct malformation involvement of the upper aerodigestive tract can cause significant functional compromise that is difficult to treat.

Lymphatic and Other Vascular Malformative/Overgrowth Disorders Are Caused by Somatic Mutations in PIK3CA

OBJECTIVES To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Childrens Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Childrens Hospital. RESULTS Most individuals from Boston Childrens Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases. Seventy-four percent of patients with LM from Seattle Childrens Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.

Furlow palatoplasty for management of velopharyngeal insufficiency: a prospective study of 148 consecutive patients.

Background: The objectives of the study were to describe speech outcomes in a large series of patients undergoing Furlow palatoplasty for management of velopharyngeal insufficiency and to test whether preoperative velopharyngeal gap size and other patient characteristics significantly affect those outcomes. Methods: Data collected included age at the time of surgery, surgeon, type of cleft, syndrome diagnosis, preoperative velopharyngeal gap size as determined by videonasendoscopy, and preoperative and postoperative perceptual speech assessments. Descriptive statistics were generated and ordinal logistic regression on the outcome variable, postoperative velopharyngeal insufficiency severity score, was performed. Results: In this series of 154 patients, 148 had complete perceptual speech data. Of these 148 patients, 72 percent had improvement in velopharyngeal insufficiency severity after the procedure and 56 percent had complete resolution of velopharyngeal insufficiency. Postoperative insufficiency was scored as none or minimal (i.e., resolution) in 38 of 52 patients (73 percent) with a small preoperative velopharyngeal gap, 26 of 51 patients (51 percent) with a moderate preoperative gap, and four of 21 patients (19 percent) with a large preoperative gap. Preoperative velopharyngeal gap size was significantly associated (p < 0.0001) with postoperative insufficiency on ordinal multivariate logistic regression after controlling for preoperative insufficiency and other covariates. There was not a significant association between syndrome diagnosis, age at Furlow palatoplasty (younger than 5 years versus older), gender, surgeon, or presence of submucous cleft palate and postoperative speech outcome, in either the unadjusted or adjusted analyses. Conclusions: Preoperative velopharyngeal gap size, as determined with nasendoscopy, was significantly associated with postoperative velopharyngeal insufficiency severity after Furlow palatoplasty. Small gap size is associated with a greater likelihood of resolution.

Head and Neck Lymphatic Malformation Treatment: A Systematic Review

Objective To systematically review literature pertaining to head and neck lymphatic malformation treatment and to use individual-level data presented in qualifying case series to describe the reported efficacy, complications, and functional impact of surgery and sclerotherapy. The authors evaluated whether treatment modalities differ by lymphatic malformation stage. Data Sources The terms lymphangioendothelioma, lymphangioma, cystic hygroma, and malformation were used to perform an Ovid literature search yielding 6292 references. The authors excluded references that did not involve head and neck lymphatic malformation treatment, include at least 5 patients, follow patients 1 year, define treatment modality, and state complications. Review Methods The authors summarized data from 1205 patients reported in 41 articles. Individual-level data, in the 29 articles reporting these data, were pooled and tabulated. Results The absence of within-study comparisons of treatment success, as well as the range of reporting methods, precluded a formal meta-analysis. Most reports were case series (37; 90%). The primary treatment modality was sclerotherapy in 17 (41%), surgery in 16 (39%), or surgery combined with other modalities in 9 (20%). Individual-level data were captured for 283 patients. No treatment modality clearly resulted in superior treatment outcome. Complications were more frequent in surgical series but were reported inconsistently in sclerotherapy studies. Conclusion There is evidence that lymphatic malformation treatment can be done effectively with surgery or sclerotherapy, but further study is necessary to determine which is superior. Standardized guidelines for reporting lymphatic malformation case series do not currently exist, making comparison of treatment outcomes of differing treatment modalities difficult.

Lymphatic malformations: Current cellular and clinical investigations

Objective: Summarize current knowledge of lymphatic malformation development, biology, and clinical outcome measures. Methods: Panel presentation of lymphatic malformation biology and measurement of head and neck malformation treatment outcomes. Results: Characterization of lymphatic malformation endothelial and stromal cells may lead to biologically based treatment. Traditionally, lymphatic malformation treatment outcomes have been measured according to reduction of malformation size. Currently, methods to measure functional outcomes following lymphatic malformation treatment are lacking. This is particularly apparent when the malformation directly involves the upper aerodigestive tract. Conclusions: The etiology and pathogenesis of head and neck lymphatic malformations are poorly understood, but understanding is improving through ongoing investigation. Reduction of lymphatic malformation size is generally possible, but further work is necessary to optimize methods for measuring therapeutic outcomes in problematic areas.

A comparison of nasendoscopy and multiview videofluoroscopy in assessing velopharyngeal insufficiency.

OBJECTIVES: 1) To compare nasendoscopy (NE) and multiview fluoroscopy (MVF) in assessing velopharyngeal gap size; and 2) to determine the relationship between these assessments and velopharyngeal insufficiency (VPI) severity. STUDY DESIGN AND SETTING: Retrospective review of consecutive patients with VPI at a tertiary care childrens hospital, assessed with NE and MVF between 1996 and 2003. RESULTS: 177 subjects. NE and MVF gap areas were correlated (R = 0.34, 95% CI 0.26-0.41). In adjusted analysis, VPI severity was associated with: 1) NE gap area (OR = 2.78, 95% CI 1.96-3.95), 2) MVF gap area (OR 1.64, 95% CI 1.37-1.95), 3) age <5 years (OR 3.30, 95% CI 1.47-7.38), and 4) previously repaired cleft palate (OR 0.48, 95% CI 0.25-0.94). CONCLUSIONS AND SIGNIFICANCE: NE and MVF assessments provide complementary information and are correlated. Both are associated with VPI severity. However, the “birds-eye view” provided by NE has a stronger correlation with VPI severity than MVF.

Endoscopic Posterior Cricoid Split and Rib Grafting in 10 Children

Objective: To report our experience with endoscopic posterior cricoid split and rib graft insertion (EPCS/RG) in children with posterior glottic (PGS) and subglottic stenosis (SGS). Design: Retrospective analysis of case series, with 1 to 2 year follow‐up. Setting: Tertiary‐care pediatric referral center. Patients: Ten consecutive patients undergoing EPCS/RG. Intervention: EPCS/RG is a new procedure that expands the posterior glottic opening by dividing the posterior cricoid lamina endoscopically with a laser and inserting a rib cartilage graft through the laryngoscope. Main Outcome Measures: Laryngeal function and hospital stay. Results: Successful decannulation in two of two patients with PGS and one of five patients with PGS and SGS without further surgery. Of the four not initially decannulated, two were decannulated with adjunctive procedures, and the other two can now tolerate tracheostomy capping for extended periods of time. We achieved improvement in exercise tolerance in three nontracheotomy‐dependent patients. For those with established tracheotomies, median hospital stay was 3 days and intensive care unit care was unnecessary. There were no major complications or deterioration of voice or feeding. Conclusions: EPCS/RG appears to be safe and effective in the management of PGS in selected pediatric patients. This minimally invasive procedure has advantages over traditional open approaches and destructive endoscopic techniques (cordotomy and arytenoidectomy). The role of EPCS/RG alone in the face of severe grades of SGS appears to be limited.