Exploring Factors Associated with Implant Removal Satisfaction in Breast Implant Illness Patients: A PRO BREAST-Q Study.

Background: Breast implant illness (BII) is a poorly understood heterogeneous disorder treated with implant removal; however, patient-reported symptoms and outcomes after treatment remain unclear. Methods: A retrospective review of patients undergoing bilateral breast implant removal related to BII by two surgeons at an academic medical center between 2018 and 2022 was conducted. Patients were surveyed using the BREAST-Q Reconstruction model with the American Society for Aesthetic Plastic Surgery BII survey extension. Outcomes were analyzed using multivariable logistic regression, adjusted for patient-associated factors. Results: Forty-seven patients were surveyed with a response rate of 51% (n = 24). Of the 20 patients who completed the survey, the majority were White (85%), with 45% (n = 9) having a documented history of psychiatric illness. Six (30%) patients had capsular contracture and four (20%) had documented implant rupture. Most implant removal procedures (n = 12, 60%) were not covered by insurance. Fourteen (70%) patients reported a net improvement in their symptoms after implant removal, most commonly chest discomfort, muscle pain, fever, and headaches. Capsular contracture was predictive of reduced psychosocial, sexual, and breast satisfaction scores (P = 0.015). Self-pay was predictive of increased breast satisfaction scores (P = 0.009), but had no impact on symptomatic improvement. A reduced time to implant removal was predictive of fewer residual symptoms (P = 0.032). Psychiatric illness had no significant impact on the outcomes. Conclusions: In the setting of suspected or diagnosed BII, a reduced time to implant removal may decrease the risk of residual symptoms and improve overall patient satisfaction. In patients with capsular contracture, preoperative counseling should emphasize that implant removal may only improve physical symptoms.

Understanding public perception of bra size.

BACKGROUND: Breast cup size is often used in conversations between patients and their surgeons to communicate about goals and expectations for postoperative results. Cup size, however, is a poorly defined concept. The goal of this study was to assess whether the perception of breast cup size is consistent in a general population of survey respondents. METHODS: A survey consisting of a demographic questionnaire, personal bra use questionnaire, and 27 de-identified preoperative images of patient's breasts was administered to 500 respondents using the Amazon MTurk platform. Survey respondents were asked to guess the cup size for each of 27 patients. RESULTS: On average, respondents correctly identified the patient's reported cup size 43.32% of the time. Male and female respondents chose the same cup size for most breast images. Survey respondents who had professional fittings were significantly less likely to accurately identify cup size (38.75% vs. 42.67%, p = 0.02). Those who had a personal history of breast surgery were also less likely to choose correctly (36.92% vs. 43.86%, p < 0.01). CONCLUSION: The results of this study suggest that the perception of cup size is broadly similar across a general population sample. However, subgroups who would be expected to have more knowledge about and experience with breast sizing-including women who have had professional bra fittings and women who have had breast surgery-differ significantly in their perception of cup size. This suggests that cup size language should be used with caution in preoperative discussions between patients and their surgeons.

Short- and Long-Term Outcomes following Severe Traumatic Lower Extremity Reconstruction: The Value of an Orthoplastic Limb Salvage Center to Racially Underserved Communities.

BACKGROUND: Previous studies have demonstrated that nonwhite race and disadvantaged socioeconomic status negatively impact outcomes following lower extremity reconstruction. The authors sought to characterize differences in outcomes between racial groups in patients necessitating traumatic lower extremity reconstruction at an orthoplastic limb salvage center. METHODS: A retrospective review between 2002 and 2019 was conducted of patients who underwent free flap lower extremity reconstruction at an orthoplastic limb salvage center. Patient demographics were identified, and permanent addresses were used to collect census data. Short-term complications and long-term functional status were recorded. RESULTS: One hundred seventy-three patients underwent lower extremity reconstruction and met inclusion criteria. Among all three groups, African American patients were more likely to be single (80 percent African American versus 49 percent Caucasian and 29.4 percent other; p < 0.05) and had significantly lower rates of private insurance compared with Caucasian patients (25 percent versus 56.7 percent; p < 0.05). African American patients demonstrated no significant differences in total flap failure (4.9 percent versus 8 percent and 5.6 percent; p = 0.794), reoperations (10 percent versus 5.8 percent and 16.7 percent; p = 0.259), and number of readmissions (2.4 versus 2.0 and 2.1; p = 0.624). Chronic pain management (53.3 percent versus 44.2 percent and 50 percent; p = 0.82), full weight-bearing status (84.2 percent versus 92.7 percent and 100 percent; p = 0.507), and ambulation status (92.7 percent versus 100 percent and 100 percent; p = 0.352) were similar among groups. CONCLUSIONS: Outcomes are equivalent between racial groups presenting to an orthoplastic limb salvage center for lower extremity reconstruction. The postoperative rehabilitation strategies, follow-up, and overall support that an orthoplastic limb salvage center ensures may lessen the impact of socioeconomic disparities in traumatic lower extremity reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Somatic PIK3CA mutations are present in multiple tissues of facial infiltrating lipomatosis.

BackgroundFacial infiltrating lipomatosis (FIL) is a congenital disorder that causes overgrowth of one side of the face. The purpose of this study was to determine whether PIK3CA mutations are present in tissues outside of the subcutaneous adipose.MethodsFIL tissues from three patients were dissected to enrich for cells from skin, subcutaneous tissue, orbicularis oris muscle, buccal fat, zygomatic bone, and mucosal neuroma. Endothelial cells within the affected tissue also were enriched using CD31 microbeads. Laser capture microdissection on formalin-fixed paraffin-embedded histologic sections was performed to collect specific cell types. DNA was extracted from each tissue and cell type, and measured for the abundance of mutant PIK3CA alleles using droplet digital PCR.ResultsWe detected mutant PIK3CA alleles in every tissue and cell type tested from each overgrown face; frequencies ranged from 1.5 to 53%. There were fewer mutant endothelial cells compared with nonendothelial cells, and the stromal cell compartment had the highest frequency of mutant cells in each tissue.ConclusionsPIK3CA mutations are not restricted to a single tissue or cell type in FIL. Overgrowth in this condition is likely due to the mutation arising in a cell that contributes to several different facial structures during embryogenesis.

Somatic MAP2K1 Mutations Are Associated with Extracranial Arteriovenous Malformation.

Arteriovenous malformation (AVM) is a fast-flow, congenital vascular anomaly that may arise anywhere in the body. AVMs typically progress, causing destruction of surrounding tissue and, sometimes, cardiac overload. AVMs are difficult to control; they often re-expand after embolization or resection, and pharmacologic therapy is unavailable. We studied extracranial AVMs in order to identify their biological basis. We performed whole-exome sequencing (WES) and whole-genome sequencing (WGS) on AVM tissue from affected individuals. Endothelial cells were separated from non-endothelial cells by immune-affinity purification. We used droplet digital PCR (ddPCR) to confirm mutations found by WES and WGS, to determine whether mutant alleles were enriched in endothelial or non-endothelial cells, and to screen additional AVM specimens. In seven of ten specimens, WES and WGS detected and ddPCR confirmed somatic mutations in mitogen activated protein kinase kinase 1 (MAP2K1), the gene that encodes MAP-extracellular signal-regulated kinase 1 (MEK1). Mutant alleles were enriched in endothelial cells and were not present in blood or saliva. 9 of 15 additional AVM specimens contained mutant MAP2K1 alleles. Mutations were missense or small in-frame deletions that affect amino acid residues within or adjacent to the protein's negative regulatory domain. Several of these mutations have been found in cancers and shown to increase MEK1 activity. In summary, somatic mutations in MAP2K1 are a common cause of extracranial AVM. The likely mechanism is endothelial cell dysfunction due to increased MEK1 activity. MEK1 inhibitors, which are approved to treat several forms of cancer, are potential therapeutic agents for individuals with extracranial AVM.

A somatic GNA11 mutation is associated with extremity capillary malformation and overgrowth.

BACKGROUND: Capillary malformation is a cutaneous vascular anomaly that is present at birth, darkens over time, and can cause overgrowth of tissues beneath the stain. The lesion is caused by a somatic activating mutation in GNAQ. In a previous study, we were unable to identify a GNAQ mutation in patients with a capillary malformation involving an overgrown lower extremity. We hypothesized that mutations in GNA11 or GNA14, genes closely related to GNAQ, also may cause capillary malformations. METHODS: Human capillary malformation tissue obtained from 8 patients that had tested negative for GNAQ mutations were studied. Lesions involved an extremity (n = 7) or trunk (n = 1). Droplet digital PCR (ddPCR) was used to detect GNA11 or GNA14 mutant cells (p.Arg183) in the specimens. Single molecule molecular inversion probe sequencing (smMIP-seq) was performed to search for other mutations in GNA11. Mutations were validated by subcloning and sequencing amplimers. RESULTS: We found a somatic GNA11 missense mutation (c.547C > T; p.Arg183Cys) in 3 patients with a diffuse capillary malformation of an extremity. Mutant allelic frequencies ranged from 0.3 to 5.0%. GNA11 or GNA14 mutations were not found in 5 affected tissues or in unaffected tissues (white blood cell DNA). CONCULSIONS: GNA11 mutations are associated with extremity capillary malformations causing overgrowth. Pharmacotherapy that affects GNA11 signaling may prevent the progression of capillary malformations.

Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain. METHODS: Two human SWS brain specimens were fractionated by fluorescence-activated cell sorting into hematopoietic (CD45), endothelial (CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2), and perivascular (platelet-derived growth factor receptor beta) cells and cells negative for all markers. The sorted cell populations were analyzed for GNAQ p.R183Q mutation by droplet digital polymerase chain reaction. SWS patient-derived brain endothelial cells were selected by anti-CD31-coated magnetic beads and cultured in endothelial growth medium in vitro. RESULTS: The GNAQ p.R183Q mutation was present in brain endothelial cells in two SWS specimens, with mutant allelic frequencies of 34.7% and 24.0%. Cells negative for all markers also harbored the GNAQ mutation. The mutant allelic frequencies in these unidentified cells were 9.2% and 8.4%. SWS patient-derived brain endothelial cells with mutant allelic frequencies of 14.7% and 21% survived and proliferated in vitro. CONCLUSIONS: Our study provides evidence that GNAQ p.R183Q mutation is enriched in endothelial cells in SWS brain lesions and thereby reveals endothelial cells as a source of aberrant Gαq signaling. This will help to understand the pathophysiology of SWS, to discover biomarkers for predicting cerebral involvement, and to develop therapeutic targets to prevent neurological impairments in SWS.

Beckwith-Wiedemann Syndrome and Primary Lymphedema of the Lower Extremity.

Beckwith-Wiedemann syndrome is the most common genetic overgrowth syndrome. Patients with Beckwith-Wiedemann syndrome may have hemihypertrophy, but their lymphatic vasculature is intact. We present a child with Beckwith-Wiedemann syndrome and lower extremity enlargement thought to be due to hemihypertrophy that was instead diagnosed with primary lymphedema. There are many causes of leg overgrowth in the pediatric population and misdiagnosis is common. While extremity enlargement secondary to hemihypertrophy may occur in 15% of patients with Beckwith-Wiedemann syndrome, progression and pitting edema only occur in primary lymphedema. This report highlights the importance of ensuring an accurate diagnosis so that patients are managed appropriately.

Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma.

Congenital hemangioma is a rare vascular tumor that forms in utero. Postnatally, the tumor either involutes quickly (i.e., rapidly involuting congenital hemangioma [RICH]) or partially regresses and stabilizes (i.e., non-involuting congenital hemangioma [NICH]). We hypothesized that congenital hemangiomas arise due to somatic mutation and performed massively parallel mRNA sequencing on affected tissue from eight participants. We identified mutually exclusive, mosaic missense mutations that alter glutamine at amino acid 209 (Glu209) in GNAQ or GNA11 in all tested samples, at variant allele frequencies (VAF) ranging from 3% to 33%. We verified the presence of the mutations in genomic DNA using a combination of molecular inversion probe sequencing (MIP-seq) and digital droplet PCR (ddPCR). The Glu209 GNAQ and GNA11 missense variants we identified are common in uveal melanoma and have been shown to constitutively activate MAPK and/or YAP signaling. When we screened additional archival formalin-fixed paraffin-embedded (FFPE) congenital cutaneous and hepatic hemangiomas, 4/8 had GNAQ or GNA11 Glu209 variants. The same GNAQ or GNA11 mutation is found in both NICH and RICH, so other factors must account for these tumors' different postnatal behaviors.

Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations.

BACKGROUND: A somatic mutation in GNAQ (c.548G>A; p.R183Q), encoding Gαq, has been found in syndromic and sporadic capillary malformation tissue. However, the specific cell type containing the mutation is unknown. The purpose of this study was to determine which cells in capillary malformations have the GNAQ mutation. METHODS: Human capillary malformation tissue was obtained from 13 patients during a clinically indicated procedure. Droplet digital polymerase chain reaction, capable of detecting mutant allelic frequencies as low as 0.1 percent, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence-activated cell sorting into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by droplet digital polymerase chain reaction. RESULTS: Eight capillary malformations contained GNAQ p.R183Q mutant cells, two lesions had novel GNAQ mutations (p.R183L and p.R183G), and three capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2 to 11 percent. Following fluorescence-activated cell sorting, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-ß-positive cell population; mutant allelic frequencies were 3 to 43 percent. CONCLUSION: Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation.

Management of Vascular Anomalies and Related Conditions Using Suction-Assisted Tissue Removal.

UNLABELLED: Vascular anomalies and related conditions cause overgrowth of tissues. The purpose of this study was to determine the efficacy and safety of liposuction techniques for pediatric overgrowth diseases. Patients treated between 2007 and 2015 who had follow-up were reviewed. Seventeen patients were included; the median age was 12.7 years. The causes of overgrowth included infiltrating lipomatosis (n = 7), capillary malformation (n = 6), hemihypertrophy (n = 1), infantile hemangioma (n = 1), lipedema (n = 1), and macrocephaly-capillary malformation (n = 1). Forty-seven percent had enlargement of an extremity, 41 percent had facial hypertrophy, and 12 percent had expansion of the trunk. All subjects had a reduction in the size of the overgrown area and improved quality of life. Suction-assisted tissue removal is an effective technique for reducing the volume of the subcutaneous compartment for patients with pediatric overgrowth diseases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Nodular Foot Myxedema Masquerading as Lymphedema.

Lymphedema results from abnormal development or injury to the lymphatic system. One-fourth of patients with lower extremity enlargement are erroneously labeled with "lymphedema." We describe a patient with hypothyroidism who developed soft-tissue overgrowth of her foot. She was referred to our Lymphedema Program for management of "lymphedema" and overgrown toes. The patient's lymphoscintigram showed normal lymphatic function in her extremities, and she was diagnosed with myxedema by histopathology. Nodular localized myxedema should be included in the differential diagnosis of lymphedema.

Circular Excision and Purse-String Closure for Pediatric Facial Skin Lesions.

Standard resection of pediatric facial skin lesions consists of lenticular excision and linear closure. This one-stage procedure for circular lesions results in a linear scar 3 times longer than the diameter of the removed specimen. Circular excision and purse-string closure has been described for infantile hemangiomas to reduce the length of scar. The purpose of this study was to analyze the application of this technique for any type of circular facial skin lesion in the pediatric population. Records of consecutive pediatric patients with facial skin lesions treated with circular excision and purse-string closure from 2007-2014 were reviewed. Patient age, sex, type of lesion, location, and size were recorded. Number of stages necessary to remove the area and complications were analyzed. Seventy-seven children (74% female) underwent circular excision and purse-string closure for an infantile hemangioma (46%), pigmented nevus (27%), Spitz nevus (7%), pilomatrixoma (5%), pyogenic granuloma (5%), vascular malformation (4%), or another type of skin lesion (6%). Age at the time of resection was 6.0 years (range 4 months-17 years) and mean lesion area was 3.9  cm (range 0.2-19.6); 30% of patients underwent a second procedure and no infection or wound dehiscence occurred. Circular excision and purse-string closure is an effective technique to manage any type of circular skin lesion in the pediatric population. It is particularly useful for lesions on the face because it limits the length of a scar. A subset of patients may benefit from second procedure to convert the circular scar from a circle into a line.

A somatic MAP3K3 mutation is associated with verrucous venous malformation.

Verrucous venous malformation (VVM), also called "verrucous hemangioma," is a non-hereditary, congenital, vascular anomaly comprised of aberrant clusters of malformed dermal venule-like channels underlying hyperkeratotic skin. We tested the hypothesis that VVM lesions arise as a consequence of a somatic mutation. We performed whole-exome sequencing (WES) on VVM tissue from six unrelated individuals and looked for somatic mutations affecting the same gene in specimens from multiple persons. We observed mosaicism for a missense mutation (NM_002401.3, c.1323C>G; NP_002392, p.Iso441Met) in mitogen-activated protein kinase kinase kinase 3 (MAP3K3) in three of six individuals. We confirmed the presence of this mutation via droplet digital PCR (ddPCR) in the three subjects and found the mutation in three additional specimens from another four participants. Mutant allele frequencies ranged from 6% to 19% in affected tissue. We did not observe this mutant allele in unaffected tissue or in affected tissue from individuals with other types of vascular anomalies. Studies using global and conditional Map3k3 knockout mice have previously implicated MAP3K3 in vascular development. MAP3K3 dysfunction probably causes VVM in humans.

Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia.

Focal malformations of cortical development, including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are important causes of intractable childhood epilepsy. Using targeted and exome sequencing on DNA from resected brain samples and nonbrain samples from 53 patients with FCD or HME, we identified pathogenic germline and mosaic mutations in multiple PI3K/AKT pathway genes in 9 patients, and a likely pathogenic variant in 1 additional patient. Our data confirm the association of DEPDC5 with sporadic FCD but also implicate this gene for the first time in HME. Our findings suggest that modulation of the mammalian target of rapamycin pathway may hold promise for malformation-associated epilepsy.

Facial wound closure in children using a 7-0 absorbable suture dressing.

BACKGROUND: Management of pediatric facial wounds is more challenging compared to adults. Suture removal is difficult, and children are less likely to protect the suture line postoperatively. The purpose of this study was to determine the efficacy of a facial wound closure regimen designed to ensure the best possible outcome in the pediatric population. METHODS: Children 12 years or younger who had a skin lesion resected from the face between 2007 and 2013 were investigated. Patients who had their wound closed using 7-0 absorbable suture, glue, and tape were studied. Predictive variables included patient age, indication for the procedure, size of the excised lesion, and location of the repair. Outcome measures were infection, wound dehiscence, and scar appearance. RESULTS: Two-hundred sixty-one children were included (151 girls, 110 boys). The mean (SD) age was 4.0 years (3.3 y). Types of lesions that were excised were nevus (24.9%), cyst (22.2%), vascular anomaly (19.5%), pilomatrixoma (13.8%), accessory tragus (11.9%), scar (4.6%), or other (3.1%). The mean (SD) area of the resected specimen was 2.2 cm(2) (3.9 cm(2)). The complication rate was 0.8% (infection, n = 1; dehiscence, n = 1). Four patients had an unfavorable appearing scar that widened (1.5%). DISCUSSION: A facial wound closure regimen using small absorbable sutures, glue, and tape optimizes outcomes in the pediatric population. Suture removal is not required, complications are rare, and scar appearance is excellent.

Management of problematic infantile hemangioma using intralesional triamcinolone: efficacy and safety in 100 infants.

BACKGROUND: Intralesional corticosteroid is one method used to limit the rapid growth of infantile hemangiomas. The purpose of this study was to determine the efficacy and safety of triamcinolone injection using a standardized protocol. METHODS: The study comprised infants managed with intralesional corticosteroid between 2007 and 2013. Tumors ≤3 cm in diameter were injected with triamcinolone, not to exceed 3 mg/kg, and followed every 4-6 weeks to determine whether additional injections were indicated. Predictive variables were patient age and tumor location, depth, and size. Treatment response was defined as regression, stabilization, or failure. Rebound growth and drug morbidity were recorded. RESULTS: Seventy-three females and 27 males had lesions located on the lip (29%), cheek (20%), nose (16%), periorbital area (13%), forehead (7%), scalp (4%), chin (2%), ear (2%), trunk (2%), extremity (2%), and neck (2%). Mean tumor size was 2.1 cm(2) (range 0.15-9.0). Treatment began at an average age of 11 weeks (range 3-30). The mean number of injections was 1.8 (range 1-5), and the average dose per injection was 1.6 mg/kg (range 0.76-2.66). All tumors responded: 63% regressed and 37% stabilized. Rebound growth affected 40% of tumors at a median of 3 weeks (IQR 3-4) following injection. Age, location, size, and depth did not affect treatment response (p = 0.7). None of the patients exhibited systemic side-effects and 2% had atrophy at the site of injection. CONCLUSION: Intralesional triamcinolone is an effective treatment for small, localized proliferating infantile hemangiomas. Therapy is safe and infants are at minimal risk for systemic side-effects when low doses of corticosteroid are used.