Aminocaproic acid administration is associated with reduced perioperative blood loss and transfusion in pediatric craniofacial surgery.

BACKGROUND: Severe blood loss is a common complication of craniofacial reconstruction surgery. The antifibrinolytic ε-aminocaproic acid (EACA) reduces transfusion requirements in children undergoing cardiac surgery and in older children undergoing spine surgery. Tranexamic acid (TXA), another antifibrinolytic with a similar mechanism of action, has been shown to reduce blood loss and transfusion requirements in children undergoing craniofacial surgery. However, TXA has been associated with an increase in post-operative seizures and is more expensive than EACA. There is currently little published data evaluating the efficacy of EACA in children undergoing craniofacial surgery. METHODS: This is a retrospective study of prospectively collected data from our craniofacial perioperative registries for children under 6 years of age who underwent anterior or posterior cranial vault reconstruction. We compared calculated blood loss, blood donor exposures, and post-operative drain output between subjects who received EACA and those who did not. RESULTS: The registry queries returned data from 152 subjects. Eighty-six did not receive EACA and 66 received EACA. The EACA group had significantly lower calculated blood loss (82 ± 43 vs. 106 ± 63 ml/kg, P = 0.01), fewer intraoperative blood donor exposures (median 2, interquartile range 1-2 vs. median 2, interquartile range 1-3; P = 0.02) and lower surgical drain output in the first post-operative 24 h (28 ml/kg vs. 37 ml/kg, P = 0.001) than the non-EACA group. CONCLUSION: In this analysis of prospectively captured observational data, EACA administration was associated with less calculated blood loss, intraoperative blood donor exposures, and post-operative surgical drain output.

Clinical care in craniofacial microsomia: a review of current management recommendations and opportunities to advance research.

Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM.

Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery.

BACKGROUND: Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery. METHODS: Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. RESULTS: Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. CONCLUSIONS: EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Clinical characteristics of patients with unicoronal synostosis and mutations of fibroblast growth factor receptor 3: a preliminary report.

Clinical teaching dictates that isolated unicoronal synostosis is sporadic in occurrence and is possibly related to intrauterine constraint. Despite this, isolated reports document a familial occurrence. It has previously been recognized that there may be a familial pattern of inheritance. Recently, mutations in fibroblast growth factor receptors (FGFRs) have been implicated in several syndromic craniosynostoses. At the authors' institution, mutations in FGFR3, located at chromosome 4p16, have been found to cause coronal synostosis. Two cases of unicoronal synostosis were found to have the same Pro250Arg missense mutation in FGFR3. This finding suggested that all patients with a diagnosis of unicoronal synostosis be screened for the FGFR3 mutation. Between January and December of 1996, patients with a diagnosis of plagiocephaly at the Children's Hospital of Philadelphia were evaluated for the FGFR3 mutation. Thirty-seven patients with unicoronal synostosis had mutational studies. Two additional patients were known to have the FGFR3 mutation at the onset of the study. Of the 37 patients screened, four were found to have the FGFR3 mutation, for a total of six patients with both unicoronal synostosis and the FGFR3 mutation. All patients with unicoronal synostosis were evaluated for facial dysmorphology and operative outcome. The six patients with the FGFR3 mutation had more severe cranial dysmorphology and were more likely to need surgical revision than those without the FGFR3 mutation. The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly. The clinical, radiologic, and molecular findings will be an important addition to the surgical management and counseling of patients with unicoronal synostosis.

A diagnostic approach to identifying submicroscopic 7p21 deletions in Saethre-Chotzen syndrome: fluorescence in situ hybridization and dosage-sensitive Southern blot analysis.

PURPOSE: To report on the use of fluorescence in situ hybridization (FISH) and dosage-sensitive Southern blot analysis in the molecular diagnosis of patients with Saethre-Chotzen syndrome. METHODS: FISH and dosage-sensitive Southern blot analysis utilizing TWIST gene probes were performed on patients with Saethre-Chotzen syndrome but without an identifiable TWIST sequence variation. RESULTS: Four unrelated patients with a deletion of the TWIST gene were identified by Southern blot; one of them had a complex chromosomal rearrangement involving 7p21 and no apparent deletion by FISH, suggesting a smaller deletion in the region including the TWIST gene. A fifth patient had an abnormal TWIST gene fragment on Southern blot analysis that segregated with the disease in the family; FISH was normal in this patient, suggesting a partial deletion or rearrangement in or near the gene. CONCLUSION: FISH and dosage-sensitive Southern blot analysis are useful diagnostic tools in Saethre-Chotzen syndrome without TWIST sequence variation.

Lip reconstruction following Mohs' surgery: the role for composite resection and primary closure.

Surgical outcomes and patient satisfaction with composite resection and primary closure for the management of upper-lip defects following Mohs' surgery were evaluated. Twenty-seven patients underwent upper-lip reconstruction following Mohs' surgery from 1993 to 1997. Twelve of these patients were selected for this report based on adequate follow-up examinations and photographs. There were nine women and three men with a mean age of 46 years (range, 33 to 70 years). Eleven patients underwent Mohs' surgery for basal cell carcinoma and one patient for squamous cell carcinoma of the upper lip. The defects varied in size and location, often extending beyond a single aesthetic subunit. The reconstruction was performed an average of 7 days after Mohs' surgery (range, 1 to 23 days). In 50 percent of the cases, a full-thickness excision was performed, which included orbicularis oris and inner-lip mucosa. The functional results were graded as near normal to normal in all cases. There were no observed changes in oral continence, eating or speech. Two patients experienced numbness medial to the operative site, but this had no adverse affect on lip function. The aesthetic results were graded as very good to excellent in all cases. Eleven of the 12 patients were satisfied with their lip appearance and function. Conventional wisdom dictates that during reconstruction of upper-lip defects, one should attempt to maintain a majority of the uninvolved tissue for the best result. Although these techniques result in wound closure, they fail to consider lip aesthetics. By using a vertically oriented composite resection of the tipper lip with the additional resection of uninvolved tissue, normal lip architecture is maintained. In our experience, this results in a superior aesthetic and functional result.

The direct effect of intraorbital pressure on orbital growth in the anophthalmic piglet.

Tissue expanders placed within the orbit can have a positive effect on orbital and ipsilateral midfacial growth. To date, there is no precise method for controlling and monitoring expansion to induce normal growth in the developing facial skeleton. The present study was undertaken to determine the optimal physiologic pressure required to stimulate normal orbital growth and to determine whether above-normal growth could be achieved with higher intraorbital pressures. Using a neonatal swine model, an accurate method of monitoring intraorbital pressure, precisely controlling intraorbital expansion, and achieving normal orbital growth was explored. Sixteen male, 3-week-old Yorkshire piglets were randomly divided into three surgical groups. In each group, the left orbit was the experimental side, and the contralateral right orbit served as an untreated control. Group 1 (n = 6) underwent enucleation only. Group 2 (n = 5) underwent enucleation and orbital expansion at a near-normal physiologic pressure of 20 mmHg. Group 3 (n = 5) underwent enucleation and orbital expansion at a supernormal pressure of 60 mmHg. Spherical tissue expanders (10 cc) with a separate injection port were utilized as the orbital expanders. Pressure was monitored by an electronic manometer that was calibrated daily. Morphology of the orbits was documented by photography, the dimensions of the orbits were quantitated by three-dimensional mechanical digitization, and orbital volumes were calculated. In the unexpanded, anophthalmic control group, a significant reduction in radial growth after evisceration was seen. In group 2, the orbit stimulated with a consistent pressure of 20 mmHg, just above the physiologic normal pressure of 17 mmHg, showed an increase in radial dimension of 8 percent compared with the unoperated side. In the high-pressure group of 60 mmHg, an increase of 16 percent in the radius was observed over the 4-week period. This led to a corresponding increase in orbital volumes with increased pressure. Utilizing a paired t test, these differences in the radial and volumetric growth of the orbit were statistically significant (p < 0.005). The results obtained demonstrated a direct relationship between intraorbital pressure and the growth of the bony orbit in the radial dimension. On the basis of this study, we concluded that orbital expansion maintained at normal physiologic pressure can stimulate normal orbital growth in the neonatal facial skeleton. In addition, application of above-normal pressures for expansion can induce accelerated orbital growth.

Analysis and treatment of severe trigonocephaly.

A retrospective analysis of seven patients with clinically severe trigonocephaly was performed, including a review of preoperative and postoperative computed tomography scans. A method of analyzing the trigonocephalic deformity was developed. This is based on determination of the angular severity of the forehead (110 +/- 4 degrees) and the length of half of the supraorbital bar (40 +/- 3 mm). This central angle was found to be relatively constant in this population. Using simple trigonometric relationships, a rationale for the alternative method of reconstruction used in these patients is presented. This technique is based on transverse expansion of the supraorbital bar, transposition of the lateral orbital rim, expansion of the temporal fossa, and recontouring the orbital aperture. As a separate consideration and step, the bony interorbital distance is widened.

Adult psychological functioning of individuals born with craniofacial anomalies.

This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.

Properties of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in the immature craniofacial skeleton.

Although extensive research regarding the treatment of calvarial defects has been done in adult models, little is known about the response in the maturing skeleton. The role of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in augmenting bone growth and repair of calvarial defects in a neonatal model is explored. Utilizing a 3-week-old neonatal swine model, bone growth into 28 calvarial defects was measured. After exposure of the calvaria in seven animals, four defects of 10 mm in diameter were created. In each animal, one defect was treated with a 10-mm disc of porous hydroxyapatite alone (Interpore 500, Interpore International), and a second defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV-6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The third defect combined an implanted hydroxyapatite disc covered by an expanded polytetrafluoroethylene membrane, whereas the fourth defect served as an untreated control. Histology and histomorphometry were performed on undecalcified specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the bone growth into the inorganic matrix provided complete osseous union in all specimens, and the amount of fibrosis was significantly lower (p < 0.02) in comparison with the control. Unexpectedly, there was significant osteoclastic resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous bone deposition and remodeling. The addition of an expanded polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an insignificant advantage in bone growth (27.3 percent versus 28.3 percent, respectively). Finally, the expanded polytetrafluoroethylene membrane alone afforded no qualitative advantage secondary to intrusion of brain and dura into the defect as well as displacement of the membrane inward during appositional growth, leading to incomplete healing of the defect with thinning of the surrounding cranial bone. Unique in this maturing model was morphologic evidence of complete union at the calvaria-hydroxyapatite interface in all specimens as well as active remodeling of the hydroxyapatite matrix. The results of this study suggest that porous hydroxyapatite may be a suitable bone substitute in maturing calvarial bone defects, achieving superior osseous integration and volumetric bone gain while undergoing concurrent resorption and remodeling.

Brain abscess as a complication of orthognathic surgery: diagnosis, management, and pathophysiology.

We present what we believe is the first case of a brain abscess resulting from orthognathic surgery reported in the literature. Although recent advances have significantly improved the treatment of brain abscesses, delays in diagnosis lead to persistent high rates of mortality. Often, the initial symptoms are vague and nonspecific. Commonly, the neurologic status of the patient deteriorates significantly before suspicion is raised and a CT scan is obtained. This case report is intended to benefit all practitioners who participate in the perioperative care of orthognathic surgery patients. Although the occurrence of a brain abscess is rare, it is hoped that this case will heighten the awareness of clinicians to this potential complication.

Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis.

The pathological evaluation of the pediatric inguinal hernia sac.

BACKGROUND: The College of American Pathologists has suggested that institutions should establish guidelines for the evaluation of the hernia sac. In addition, some states require the submission of this tissue for pathological evaluation. Yet, neither evidence-based guidelines nor published reviews for the evaluation of the pediatric hernia sac are available. Therefore, this retrospective study was conducted to document experience with the evaluation of the pediatric hernia sac. METHODS: All reports of the evaluation of hernia sacs submitted to the Department of Pathology during an 8-year period were reviewed. The case of any report that differed in any way from "consistent with hernia sac" was evaluated for the effect of the findings on the clinical course. RESULTS: A total of 7,924 hernia sacs were submitted on 6,034 patients. Microscopic evaluation was performed on 534. A total of 7,567 (95.4%) submitted specimens on 5,743 patients were "consistent with hernia sac" and demonstrated no other findings. Three hundred fifty-seven specimens contained findings in addition to hernia sac. In no patient did the results of the evaluation have an effect on the patient care. CONCLUSIONS: There is strong evidence that the routine pathological evaluation of pediatric hernia sacs offers little relevant clinical information. Mandatory tissue submission of hernia sacs should be reconsidered.

Bigger is not always better: body image dissatisfaction in breast reduction and breast augmentation patients.

This study investigated body image dissatisfaction in breast reduction and breast augmentation patients. Thirty breast reduction and 30 breast augmentation patients completed two body image measures preoperatively. Breast reduction patients reported greater dissatisfaction with their overall body image as compared with breast augmentation patients, part of which can be understood as a function of their increased body weight. When asked specifically about their breasts, reduction patients displayed increased body image dysphoria and maladaptive behavioral change, including embarrassment about their breasts in public areas and social settings and avoidance of physical activity. Results are discussed in the context of ideal body weight cutoffs by third-party payers for reimbursement for breast reduction. Recommendations for reimbursement criteria that de-emphasize the role of body weight are made.

Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.

To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and 33 were negative for this mutation. In three mutation positive patients with full parental studies, a parent with an extremely mild phenotype was found to carry the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. Because it is impossible to predict the FGFR3 Pro250Arg mutation status based on clinical examination alone, all patients with unicoronal synostosis should be tested for it. To assess their recurrence risk, all parents of mutation positive patients should be tested regardless of their clinical findings, because the phenotype can be extremely variable and without craniosynostosis.

Infections in craniofacial surgery: a combined report of 567 procedures from two centers.

This retrospective review of infectious complications was undertaken at two craniofacial centers (Dallas and Philadelphia). Fourteen infections were identified over a 6.5-year period in 567 intracranial procedures primarily for craniosynostosis. There were no infections in infants under 13 months of age and no cases of meningitis. The overall infection rate was 2.5 percent, and 85 percent of infections occurred in secondary reoperative cases. Tracheostomies were not identified as a risk factor for infection. No difference was found in infection rates between patients with shaved and unshaved scalps. Candida and Pseudomonas were the two most common organisms identified, and 28 percent of our infections involved yeast. The average time to diagnose infection was 11.5 days (excluding three patients who averaged 5 months). Thirteen of the fourteen infections were treated surgically with placement of a subgaleal irrigation/drainage system. Initial bony debridement was kept to a minimum. Based on our findings, recommendations are made to further lower infection rates, particularly those caused by opportunistic organisms.

Serratus anterior free-tissue transfer: harvest-related morbidity in 34 consecutive cases and a review of the literature.

Donor-site morbidity in serratus anterior free-tissue transfers is investigated in 34 consecutive cases. Nineteen lower-extremity reconstructions and 15 facial reconstructions were retrospectively analyzed. office and hospital charts were reviewed, and patients were given a follow-up questionnaire. The mean operative time was 6.3 hr and the mean estimated blood loss was 441 cc. Transfusion was required in 24 percent of cases. The early complication rate was 21 percent consisting of 6 percent hematomas and 15 percent seromas. Scar appearance, pain, numbness, and shoulder strength and mobility were acceptable. Scapular winging was detectable in 3/9 patients examined, but symptomatic in only one. The number of muscle slips harvested or whether the graft was innervated did not significantly affect this rate. Half of the patients had returned to work or school. None attributed any work disability to their donor sites. They participated in many athletic activities, including those requiring upper extremity strength and dexterity. Previously reported series are discussed, and the morbidity of this donor site is compared with reported series of other free muscle flaps. The authors find this flap useful for facial reanimation and for soft-tissue coverage with minimal bulk. Low rates of operative, perioperative, and long-term morbidity are definite advantages.

Avoiding pitfalls and managing complications of aesthetic contouring of the craniofacial skeleton.

Contouring of the facial skeleton has become applicable to a wide spectrum of patients. Although complications do occur, they now can be managed in a safe and predictable fashion. Moreover, it has been our experience that through increased use and attention to the tenets described in this article, the incidence of postoperative complications is significantly reduced.

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis.