Hearing Loss in Children With Craniofacial Microsomia.

OBJECTIVE: To evaluate the association between craniofacial phenotype and hearing loss in children with craniofacial microsomia. DESIGN: Retrospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS: Individuals with craniofacial microsomia. MAIN OUTCOME MEASURES: Ear-specific audiograms and standardized phenotypic classification of facial characteristics. RESULTS: A total of 79 participants were included in the study. The mean age was 9 years (range, 1 to 23 years) and approximately 60% were boys. Facial anomalies were bilateral in 39 participants and unilateral in 40 participants (24 right, 16 left). Microtia (hypoplasia of the ear) was the most common feature (94%), followed by mandibular hypoplasia (76%), soft tissue deficiency (60%), orbital hypoplasia or displacement (53%), and facial nerve palsy (32%). Sixty-five individuals had hearing loss (12 bilateral and 53 unilateral). Hearing loss was conductive in 73% of affected ears, mixed in 10%, sensorineural in 1%, and indeterminate in 16%. Hypoplasia of the ear or mandible was frequently associated with ipsilateral hearing loss, although contralateral hearing loss occurred in 8% of hemifaces. CONCLUSIONS: Hearing loss is strongly associated with malformations of the ipsilateral ear in craniofacial microsomia and is most commonly conductive. Hearing loss can occur contralaterally to the side with malformations in children with apparent hemifacial involvement. Children with craniofacial microsomia should receive early diagnostic hearing assessments.

Phenotypic characterization of epibulbar dermoids.

The purpose of this study was to characterize the phenotypic presentation, clinical course, and outcomes of epibulbar dermoids (EpDs) which are the most common congenital eye tumor in children. Sixty-eight dermoids were identified in 58 eyes of 48 patients of Seattle Children's Hospital between 1981 and 2014 via electronic medical record search. Patients were organized into: "EpD-Only" [patients without other congenital anomalies (n = 13)], "EpD-CFM" [patients with a craniofacial microsomia (CFM) diagnosis (n = 25)], and "EpD-Other" [patients with other congenital anomalies (n = 10)]. All EpD in the EpD-Only group were unilateral and singular, while the EpD-CFM group had six cases with multiple unilateral EpD and five cases with bilateral EpD. In the EpD-Only group, 69 % of EpD were left sided, whereas in the EpD-CFM group, there was no side predisposition. Among both groups, the majority of EpD were limbal or lipodermoids in the inferotemporal quadrant of the eye. Surgery was more common and at a younger age in the EpD-CFM group than the EpD-Only group (56 vs. 38 %, 5.2 vs. 7.0 years). Follow-up surgeries occurred only in the EpD-CFM group (21 %). EpDs were most commonly associated with preauricular tags, congenital heart defects, genitourinary, and nervous system anomalies. Whereas the location and type of EpDs did not significantly differ between the groups, the phenotype in the EpD-Only group appears to be less complex. This may indicate an important difference between EpDs in isolation and those within CFM. Additional studies will further characterize these phenotypes and outcomes.

Optimizing Surgical Treatment of Internationally Adopted Children With Cleft Lip and/or Palate: Understanding the Family Experience.

OBJECTIVE: To understand the experience of families with children undergoing cleft surgery following adoption from a country outside the United States. To identify factors, including the timing of surgery, that influence family function throughout the surgical experience. DESIGN: Semistructured qualitative interviews were conducted with parents of internationally adopted children postrepair of cleft lip and/or cleft palate and coded by a multidisciplinary study team. Mixed methods were used to contextualize themes derived from the parent interviews. RESULTS: Twenty parent interviews were conducted, and four core themes were identified: (1) parental anxieties prior to surgery, (2) considerations for the timing of surgery, (3) impact of the surgical experience on the child and family, and (4) modifiable sociocontextual factors. Parents considered a strong child bond with at least one parent and the ability of the child to communicate basic needs to be important before undergoing surgery. In retrospect, parents generally felt that the surgical experience did not have a negative impact on their child or their families and that the surgical experience may have even facilitated bonding and attachment with their child. Acceleration of family bonding was expressed more often by parents of children who were adopted at older than 2 years. CONCLUSIONS: In our study, parents reported that cleft surgery soon after international adoption did not appear to impair child bonding or adjustment. Specific family and provider factors that could optimize the experience for families were identified.

Phenotypic sub-grouping in microtia using a statistical and a clinical approach.

The clinical presentation of microtia varies widely from minimal morphological abnormalities to complete absence of the ear. In this study we sought to identify and characterize sub-groups of microtia using a statistical and a clinical approach. Photographs of 86 ears were classified in relation to all the external ear components. We used cluster analysis and rater's clinical opinion to identify groups with similar phenotypes in two separate analyses. We used Cramer's Phi coefficient of association to assess the similarity among the clinician's groupings as well as among the statistical sub-phenotypic groups and each of the clinician's groupings. The cluster analysis initially divided the 86 ears into a more and a less severe group. The less severe group included two sub-groups that included ears classified as normal and a group that had very few anomalous components. The group of 48 more affected ears all had abnormalities of the helix crus; antihelix-stem, -superior crus and -inferior crus; and antitragus. These were further divided into 4 sub-phenotypes. There was a moderate degree of association among the raters' groupings (Cramer's Phi: 0.64 to 0.73). The statistical and clinical groupings had a lower degree of association (Cramer's Phi: 0.49 to 0.58). Using standardized characterization of structural abnormalities of the ear we identified six distinct phenotypic groups; correlations with clinicians' groupings were moderate. These clusters may represent groups of ear malformations associated with the same etiology, similar time of insult or target cell population during embryonic development. The results will help inform investigations on etiology.

The Furlow palatoplasty for velopharyngeal dysfunction: velopharyngeal changes, speech improvements, and where they intersect.

OBJECTIVE: We investigated how Furlow palatoplasty changes velopharyngeal morphology and speech characteristics, as well as how the anatomical and clinical results might be related. We hypothesized that Furlow palatoplasty would result in measurable velar elongation, tightening of the genu angle, and retropositioning of the levator sling and that the achievement of these modifications might be associated with clinical speech improvement. DESIGN: Retrospective analysis of preoperative and postoperative videofluoroscopic and speech data. SETTING: Tertiary care center. PATIENTS/PARTICIPANTS: A total of 29 patients with velopharyngeal insufficiency in the setting of previous cleft palate repair or submucous cleft palate. INTERVENTIONS: Furlow palatoplasty for treatment of velopharyngeal insufficiency. OUTCOME MEASURES: Lateral videofluoroscopy and perceptual speech examination were conducted preoperatively and postoperatively in order to measure velopharyngeal dimensions and speech quality. We describe anatomical and speech changes associated with the Furlow palatoplasty and undertake an exploratory analysis of the relationship between surgical changes to the velopharynx and clinical outcomes. RESULTS: Furlow palatoplasty results in significant velar elongation, increased acuity of the genu angle, and retropositioning of the levator sling. Postoperative speech improvement was identified on the three subscales of resonance, nasal emission, and stops/plosives. Speech improvement and the absence of need for reoperation were most consistently associated with tightening of the genu angle. CONCLUSIONS: Furlow palatoplasty lengthens the palate, while both tightening and retropositioning the levator sling. These changes reflect transverse recruitment of lateral velar tissues, along with transverse tightening and anterior release of the muscle fibers, respectively. Levator tightening is most consistently associated with improved speech outcomes.

Use of antihypertensive medications and breast cancer risk.

PURPOSE: Use of specific antihypertensive medications (AHTs) has been hypothesized to increase breast cancer risk, but results across published studies are inconsistent. METHODS: We re-evaluated the relationship between AHT use and breast cancer risk in a prospective cohort of 3,201 women ≥65 years of age at recruitment now with more than double the length of follow-up (12 vs. 5 years) and substantially more breast cancer diagnoses (188 compared with 75 cases). We estimated the association between AHT use overall as well as use of specific formulations (based on data collected annually) and breast cancer risk using multivariate-adjusted Cox regression. RESULTS: Compared with women who reported no use of AHTs, women who had used calcium channel blockers (CCB) within the past two years had a 1.6-fold increased risk of breast cancer (95 % confidence interval (CI): 1.0-2.5), and in particular, recent users of immediate-release CCBs had a 2.4-fold increased risk (95 % CI: 1.3-4.5). Neither ever nor recent use of any other type of AHT was associated with breast cancer risk. CONCLUSIONS: While the observed association between immediate-release CCBs and breast cancer risk is based on a small sample size and needs to be interpreted cautiously, this result is consistent with others in the literature. However, given declines in use of these preparations in favor of sustained-release CCBs, which was not related to risk, the potential clinical and public health impact of this association is limited. This study also adds to the evidence that other commonly used AHTs are not strongly related to breast cancer risk.

Interrater reliability of a phenotypic assessment tool for the ear morphology in microtia.

The Elements of Morphology Standard Terminology working group published standardized definitions for external ear morphology. The primary objective of our study was to use these descriptions to evaluate the interrater reliability for specific features associated with microtia. We invited six raters from three different subspecialities to rate 100 ear photographs on 32 features. We calculated overall and within specialty and professional experience intraclass correlation coefficients (ICC) and 95% confidence intervals. A total of 600 possible observations were recorded for each feature. The overall interrater reliability ranged from 0.04 (95% CI: 0.00-0.14) for the width of the antihelix inferior crus to 0.93 (95% CI: 0.91-0.95) for the presence of the inferior crux of the antihelix. The reliability for quantitative characteristics such as length or width of an ear structure was generally lower than the reliability for qualitative characteristics (e.g., presence or absence of an ear structure). Categories with very poor interrater reliability included anti-helix inferior crux width (0.04, 95% CI: 0.00-0.14), crux helix extension (0.17, 95% CI 0.00-0.37), and shape of the incisura (0.14, 95% CI: 0.01-0.27). There were no significant differences in reliability estimates by specialty or professional experience for most variables. Our study showed that it is feasible to systematically characterize many of structures of the ear that are affected in microtia. We incorporated these descriptions into a standardized phenotypic assessment tool (PAT-Microtia) that might be used in multicenter research studies to identify sub-phenotypes for future studies of microtia.

Risk factors and demographics for microtia in South America: a case-control analysis.

BACKGROUND: The etiopathogenesis of microtia is still unknown in the majority of the cases, particularly for individuals presenting with isolated microtia. Our aim was to evaluate potential risk factors for this condition using a case-control approach. METHODS: We analyzed data from 1,194 live births with isolated microtia enrolled in the ECLAMC study (Estudio Colaborativo Latino Americano de Malformaciones Congénitas) from 1982 to 2011 and their respective controls. Odds ratios (ORs) were estimated with logistic regression models along with 95% confidence intervals for the resulting OR estimates controlling for the effects of potential confounders (sex, maternal age, hospital, and year of birth) for an adjusted OR (aOR). RESULTS: Multiparity was associated with a higher risk of microtia compared with primiparity (aOR, 1.5; 95% confidence interval [CI], 1.2-1.8), with women who had eight or more prior pregnancies having the highest risk (aOR, 2.8; 95% CI, 1.6-5.2). Women who presented with cold-like symptoms were at higher risk for microtia (aOR, 2.2; 95% CI, 1.2-3.9) as well as those that used tobacco or alcohol during pregnancy (aOR, 1.7; 95% CI, 1.1-2.6 and aOR, 1.4; 95% CI, 0.9-2.1, respectively). The association with alcohol use appeared to be limited to those women who reported binge drinking during pregnancy (aOR, 1.4; 95% CI, 0.7-3.1). Cases from hospitals at low altitude (<2500 m) tended to have more severe types of microtia than those from hospitals at high altitude. CONCLUSION: These results support the hypothesis that, in addition to teratogens, other nongenetic risk factors contribute to the occurrence of isolated microtia.

Making the diagnosis: metopic ridge versus metopic craniosynostosis.

INTRODUCTION: The metopic suture is the only calvarial suture which normally closes during infancy. Upon closure, a palpable and visible ridge often forms which can be confused with metopic craniosynostosis. Metopic ridging (MR) is treated nonsurgically while metopic craniosynostosis (MCS) is treated surgically. Differentiating between the two is paramount; however, consensus is lacking about where a clear diagnostic threshold lies. The goal of this study is to describe the physical examination and CT scan characteristics which may help to differentiate between physiological closure of the metopic suture with ridging (MR) and MCS. METHODS: A retrospective chart review of all patients seen at Seattle Children's Hospital between 2004 and 2009 with the diagnosis of either MCS or MR (n = 282) was performed. Physical examination characteristics described by diagnosing practitioners were analyzed. Clinical photos were assessed by 3 expert raters to determine the importance of these characteristics. CT scan findings were abstracted and compared between the two diagnoses. RESULTS: The "classic" triad of narrow forehead, biparietal widening, and hypotelorism was present in only 14% of patients with MCS. Ninety-eight percent of patients in both groups had a palpable metopic ridge. The photographic finding of narrow forehead and pterional constriction was present in all patients with MCS, but only in 11.2% and 2.8% of patients with MR. On CT scan, the presence of 3 or more MCS findings was diagnostic of MCS in 96% of patients. Patients with MCS were more likely to present before 6 months of age (66% vs. 32%). CONCLUSIONS: Patients with MCS tend to present earlier than those with MR. Upon physical examination, the relationship between the lateral frontal bone and the lateral orbit is important in distinguishing between the two diagnoses. A CT scan can be helpful in making the diagnosis not to confirm a closed suture but to identify 3 or more MCS characteristics.

Comparison of two-dimensional and three-dimensional images for phenotypic assessment of craniofacial microsomia.

Background and Purpose : Three-dimensional surface imaging is used in many craniofacial centers. However, few data exist to indicate whether such systems justify their cost. Craniofacial microsomia is associated with wide phenotypic variability and can affect most facial features. The purpose of this study is to compare three-dimensional versus two-dimensional images for classification of facial features in individuals with craniofacial microsomia. Methods : We obtained a series of two-dimensional and three-dimensional images of 50 participants, aged 0-20 years, diagnosed with craniofacial microsomia, microtia, or Goldenhar syndrome. Three clinicians classified the craniofacial features on each image, and ratings were compared by calculating kappa statistics. We also evaluated image quality using a 5-point Likert scale. Results : Reliability estimates were high for most features using both two-dimensional and three-dimensional image data. Our three-dimensional protocol did not allow for scoring of facial animation, occlusal cant, or tongue anomalies. Image quality scores for the mandible and soft tissue assessment were higher for three-dimensional images. Raters preferred two-dimensional photographs for assessment of the ear, ear canal, and eyes. Conclusions : Both three-dimensional and two-dimensional images provide useful data for objective characterization of the craniofacial features affected in craniofacial microsomia. A series of two-dimensional images has relative advantages for assessment of some specific features, such as the ear, though three-dimensional images may have advantages for quantitative analysis and qualitative assessment of deformities of the jaw and soft tissue. These results should apply to any assessment of these features with or without a craniofacial microsomia diagnosis.

Evaluation of ICD-9-CM codes for craniofacial microsomia.

BACKGROUND: Craniofacial microsomia (CFM) is a congenital condition characterized by microtia and mandibular underdevelopment. Healthcare databases and birth defects surveillance programs could be used to improve knowledge of CFM. However, no specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code exists for this condition, which makes standardized data collection challenging. Our aim was to evaluate the validity of existing ICD-9-CM codes to identify individuals with CFM. METHODS: Study sample eligibility criteria were developed by an expert panel and matched to 11 ICD-9-CM codes. We queried hospital discharge data from two craniofacial centers and identified a total of 12,254 individuals who had ≥1 potentially CFM-related code(s). We reviewed all (n = 799) medical records identified at the University of North Carolina (UNC) and 500 randomly selected records at Seattle Children's Hospital (SCH). Individuals were classified as a CFM case or non-case. RESULTS: Thirty-two individuals (6%) at SCH and 93 (12%) at UNC met the CFM eligibility criteria. At both centers, 59% of cases and 95% of non-cases had only one code assigned. At both centers, the most frequent codes were 744.23 (microtia), 754.0 and 756.0 (nonspecific codes), and the code 744.23 had a positive predictive value (PPV) >80% and sensitivity >70%. The code 754.0 had a sensitivity of 3% (PPV <1%) at SCH and 36% (PPV = 5%) at UNC, whereas 756.0 had a sensitivity of 38% (PPV = 5%) at SCH and 18% (PPV = 26%) at UNC. CONCLUSIONS: These findings suggest the need for a specific CFM code to facilitate CFM surveillance and research.

Diabetes and endometrial cancer: an evaluation of the modifying effects of other known risk factors.

To determine whether risk of endometrial cancer among women with type 2 diabetes differs with respect to other endometrial cancer risk factors, the authors used data from a population-based case-control study (1,303 cases and 1,779 controls) conducted in western Washington State during 1985-1999. History of type 2 diabetes was associated with endometrial cancer (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.2, 2.3), more strongly among women with a recent diabetes diagnosis (<5 years) (OR = 2.6, CI: 1.5, 4.7) than among those with a more distant diagnosis (> or =5 years) (OR = 1.3, CI: 0.8, 1.9). Type 2 diabetes was associated with endometrial cancer among women with a body mass index (BMI) (weight (kg)/height (m)(2)) less than 35 but not among women with a BMI of 35 or more. The observed associations persisted after finer adjustment for BMI to control for residual confounding. History of diabetes was associated with a twofold increased risk of endometrial cancer among hypertensive women, but no association was observed among nonhypertensive women. The risk associated with type 2 diabetes appeared not to vary greatly with respect to other endometrial cancer risk factors. These results support the hypothesis that type 2 diabetes is associated with endometrial cancer irrespective of the presence of other risk factors for this disease, except possibly hypertension and extreme obesity.

Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.

OBJECTIVE: The purpose of this study was to assess whether endometrial cancer risk among long-term users of (1) sequential estrogen plus progestin 10-24 days per month exceeds that of nonusers and (2) daily estrogen plus progestin (continuous combined hormone therapy) is below that of nonusers. STUDY DESIGN: In this population-based case-control study with 1038 endometrial cancer cases diagnosed in 1985-1999 and 1453 control subjects, exclusive users of a single form of hormone therapy were compared with never users of hormone therapy. RESULTS: For sequential therapy, only long-term use (> or = 6 years) was associated with increased risk (odds ratio, 2.0; 95% CI, 1.2-3.5). Continuous combined therapy was associated with decreased risk (odds ratio, 0.59; 95% CI, 0.40-0.88), with no increased risk among long-term users (odds ratio, 0.77; 95% CI, 0.45-1.3). CONCLUSION: These results support the hypotheses that continuous combined therapy does not increase (and may decrease) endometrial cancer risk and that long-term sequential therapy can lead to a modest increased risk. However, the collective results of all studies of these questions and their clinical implications remain unclear.

Reliable classification of facial phenotypic variation in craniofacial microsomia: a comparison of physical exam and photographs.

BACKGROUND: Craniofacial microsomia is a common congenital condition for which children receive longitudinal, multidisciplinary team care. However, little is known about the etiology of craniofacial microsomia and few outcome studies have been published. In order to facilitate large, multicenter studies in craniofacial microsomia, we assessed the reliability of phenotypic classification based on photographs by comparison with direct physical examination. METHODS: Thirty-nine children with craniofacial microsomia underwent a physical examination and photographs according to a standardized protocol. Three clinicians completed ratings during the physical examination and, at least a month later, using respective photographs for each participant. We used descriptive statistics for participant characteristics and intraclass correlation coefficients (ICCs) to assess reliability. RESULTS: The agreement between ratings on photographs and physical exam was greater than 80 % for all 15 categories included in the analysis. The ICC estimates were higher than 0.6 for most features. Features with the highest ICC included: presence of epibulbar dermoids, ear abnormalities, and colobomas (ICC 0.85, 0.81, and 0.80, respectively). Orbital size, presence of pits, tongue abnormalities, and strabismus had the lowest ICC, values (0.17 or less). There was not a strong tendency for either type of rating, physical exam or photograph, to be more likely to designate a feature as abnormal. The agreement between photographs and physical exam regarding the presence of a prior surgery was greater than 90 % for most features. CONCLUSIONS: Our results suggest that categorization of facial phenotype in children with CFM based on photographs is reliable relative to physical examination for most facial features.

Maternal and infant factors associated with infancy-onset hydrocephalus in Washington State.

OBJECTIVE: Hydrocephalus, a complex condition characterized by progressive accumulation of cerebrospinal fluid within the ventricular system of the brain, affects ∼ 6 in 10,000 infants and is heterogeneous in nature. Previous investigations of risk factors have not considered etiologic heterogeneity. METHODS: We conducted a case-control study of 1748 children with hydrocephalus identified through birth certificate check boxes and ICD-9 codes of linked hospital discharge records through the first year of life. Control infants were identified from birth records (N = 19,700), frequency matched to cases by year of birth. Three mutually exclusive, nonexhaustive subgroups were identified: hydrocephalus associated with a neural tube defect (n = 332); prenatal-onset hydrocephalus (n = 402); and hydrocephalus associated with intracranial hemorrhage (n = 446). Within each group, we examined associations with maternal age, race/ethnicity, parity, diabetes and hypertension, and infant sex and gestation. We used logistic regression to calculate odds ratios and 95% confidence intervals. RESULTS: Asian ethnicity was independently associated with an inverse risk of all subtypes of hydrocephalus (hydrocephalus associated with a neural tube defect: odds ratio, 0.44; 95% confidence interval, 0.23 to 0.84; prenatal-onset hydrocephalus: odds ratio, 0.47; 95% confidence interval, 0.27 to 0.83; hydrocephalus associated with intracranial hemorrhage: odds ratio, 0.59; 95% confidence interval, 0.33 to 1.07) compared with whites. Pre-existing diabetes was associated to varying degrees with all three subtypes (hydrocephalus associated with a neural tube defect: odds ratio, 1.94; 95% confidence interval, 0.61 to 6.17; prenatal-onset hydrocephalus: odds ratio, 5.20; 95% confidence interval, 2.60 to 10.40; hydrocephalus associated with intracranial hemorrhage: odds ratio, 5.26; 95% confidence intervals, 2.85 to 9.69). Hypertension had a positive association with hydrocephalus associated with intracranial hemorrhage (odds ratio, 1.91; 95% confidence interval, 1.46 to 2.52) but an inverse association with hydrocephalus associated with a neural tube defect (odds ratio, 0.59; 95% confidence interval, 0.36 to 0.98). Gestation ≤ 30 weeks was associated with all three subgroups, most notably hydrocephalus associated with intracranial hemorrhage (odds ratio, 443.56; 95% confidence intervals, 326.34 to 602.87); nearly two-thirds (64%) of hydrocephalus associated with intracranial hemorrhage infants were born ≤ 30 weeks. Male gender was independently associated only with hydrocephalus associated with intracranial hemorrhage (odds ratio, 1.82; 95% confidence interval, 1.40 to 2.39). No associations were observed with advanced or young maternal age or with parity. CONCLUSIONS: The different risk profiles seen among these three subgroups support the biologically heterogeneous nature of infantile hydrocephalus. Future research should take specific etiologic subtypes into account.

Adopted children with cleft lip and/or palate: a unique and growing population.

BACKGROUND: Standard clinical pathways are well established for children with cleft lip and/or palate. Treatment of internationally adopted children differs because of the late age at presentation, a newly evolving child-family relationship, and variable extent and quality of previous treatment. METHODS: The authors characterized the presentation and treatment patterns of all internationally adopted children with clefts at their institution between 1997 and 2011. RESULTS: Among 1841 children with clefts, 216 (12 percent) were internationally adopted: 78 percent had cleft lip and palate, 18 percent had cleft lip, and 4 percent had cleft palate. Patients originated predominantly from China (80 percent). Median age at presentation was 31 months, and the rate of new presentations increased five-fold during the study period. Eighty-two percent presented with prior cheiloplasty, and revision was recommended for 64 percent of them. Thirty-seven percent of patients had prior palatoplasty, of which 34 percent presented with a palatal fistula. Secondary palatoplasty/pharyngoplasty was performed more frequently for patients who underwent primary palatoplasty before adoption than after adoption (95 percent CI, 0.20 to 0.77). Overall, adoptees required secondary surgery more often than nonadoptees (49 percent versus 28 percent) regardless of where their primary surgery was performed. Changes in adoptee growth indices suggested improvements in systemic health following adoption. CONCLUSIONS: Internationally adopted children with clefts have unique treatment challenges. Children with unrepaired clefts undergo surgery late, and children with prior repairs frequently undergo revision. Compared with nonadoptees, adoptees require more revisions and have a higher fistula rate. Further detailed study is important to optimize care.

Clinical characteristics and surgical decision making for infants with metopic craniosynostosis in conjunction with other congenital anomalies.

BACKGROUND: Metopic craniosynostosis can occur in isolation or in conjunction with other congenital anomalies. The surgical decision making and outcomes between these 2 groups are analyzed. METHODS: A retrospective review of all children evaluated in the craniofacial clinic at Seattle Children's Hospital for metopic craniosynostosis between 2004 and 2009 was performed. Physical examination and CT scan characteristics were analyzed as were the treatment decisions and surgical outcomes. RESULTS: From 2004 to 2009, 282 patients were evaluated and 100 were determined to have metopic craniosynostosis. Of these, 19 patients were found to have additional congenital anomalies. Review of these patients' CT scans revealed 13 with classic trigonencephaly, 3 with microcephaly, and 3 with narrow frontal bones, abnormal orbits, and small anterior fossa. Patients (90%) with isolated metopic craniosynostosis underwent cranial vault expansion, whereas only 63% of the complex group did so. The complex metopic group had a longer hospital stay (5 d vs 3.4 d), more intraoperative complications, and required more repeat surgery. CONCLUSION: Patients with metopic craniosynostosis and additional anomalies require special consideration when deciding upon surgical intervention and should be cared for by a multidisciplinary team to address their additional needs.

Endometrial cancer risk in estrogen users after switching to estrogen-progestin therapy.

OBJECTIVE: It is unknown whether postmenopausal unopposed estrogen users are better off, in terms of endometrial cancer risk, switching to a combined estrogen-progestin regimen or stopping hormone use altogether. METHODS: We analyzed data from a series of three population-based case-control studies in western Washington state during 1985-1999, comparing proportions of "switchers" and "stoppers" in cases and controls. We also assessed whether the risk of endometrial cancer in either group of former unopposed estrogen users returned to that of never users. RESULTS: After multivariate adjustment using unconditional logistic regression, women who switched to a combined regimen with a progestin added for at least ten days/month (37 cases, 47 controls) had half the risk of endometrial cancer of women who stopped hormone use altogether (86 cases, 78 controls) (adjusted odds ratio = 0.5, 95% confidence interval: 0.3-1.1). Most subgroups of former users, whether they switched or stopped, had some increased risk of endometrial cancer compared to never users. CONCLUSIONS: Results from this study suggest that unopposed estrogen users may reduce their risk of endometrial cancer more by switching to a combined regimen with progestin added for at least ten days/month than by stopping hormone use altogether.

Risk of invasive breast carcinoma among women diagnosed with ductal carcinoma in situ and lobular carcinoma in situ, 1988-2001.

BACKGROUND: Incidence rates of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have been rising, but little is known about which patients will develop invasive breast cancer or what types of tumors these patients may develop. METHODS: By using Surveillance, Epidemiology and End Results (SEER) data, the authors evaluated how types of invasive breast cancers diagnosed among 37,692 DCIS and 4490 LCIS patients differed and how clinical characteristics influenced subsequent breast cancer risk. RESULTS: Among DCIS patients, incidence rates of ipsilateral and contralateral invasive breast cancer were 5.4/1000 person-years and 4.5/1000 person-years, respectively; and among LCIS patients, incidence rates were 7.3/1000 person-years and 5.2/1000 person-years, respectively. LCIS patients were 5.3-fold more likely than DCIS patients to develop invasive lobular carcinomas. Women whose DCIS had comedo histologic features or was poorly differentiated had 1.4-fold and 2.0-fold elevations in ipsilateral invasive breast cancer risk. Furthermore, among DCIS patients, 20-49 year-olds and black women and Hispanic white women had 1.6, 2.7, and 2.3-fold elevated risks of Stage III/IV breast cancer compared with 50-59 year-olds and non-Hispanic whites, respectively. CONCLUSIONS: Screening young DCIS patients more frequently and improving the follow-up care of blacks and Hispanic whites with DCIS may reduce their risk of advanced-stage breast cancer. In addition, LCIS may be a precursor rather than just an ambiguous risk factor for invasive breast cancer, and, therefore, localized treatment for LCIS may be warranted. Given that incidence rates of DCIS and LCIS have been rising, investigations of these tumors should be continued to better understand their etiology and appropriate clinical management.

Risk factors for the incidence of endometrial cancer according to the aggressiveness of disease.

There is a wide range of aggressiveness of endometrial tumors, some being indolent and easily treated while others metastasize and prove fatal. The authors used data from three population-based, case-control studies to determine if etiologic factors differ for aggressive disease. Interview data were obtained from 1,304 female residents of western Washington State who were 45-74 years of age and diagnosed with endometrial cancer during 1985-1991, 1994-1995, and 1997-1999 and from 1,779 controls who were of similar ages and selected primarily by random digit dialing. As a means of gauging aggressiveness, tumor characteristics were abstracted from the population-based cancer registry that serves western Washington State. The risk of endometrial cancer among long-term users (> or = 8 years) of unopposed estrogens was particularly high for the least aggressive tumors (odds ratio = 18.6, 95% confidence interval: 12.2, 28.6) but was elevated for moderate and highly aggressive tumors as well (odds ratios = 6.6 and 7.1, respectively). Women who were obese, had a history of diabetes, and had fewer than two children were also at increased risk, regardless of tumor aggressiveness, while oral contraceptive users were at decreased risk of only relatively more aggressive disease. In general, a woman's risk of endometrial cancer appears to be influenced by similar risk factors regardless of disease severity.