Search

Background: The purpose of this study was to determine whether augmentation mammaplasty, implant type, and implant location affect breast cancer detection, stage, and treatment., Methods: An institutional case-control study was performed of patients with prior breast augmentation undergoing breast cancer treatment from 2000 to 2013. Controls were propensity matched and randomized, and data were retrospectively reviewed., Results: Forty-eight cases and 302 controls were analyzed. Palpable lesions were detected at a smaller size in augmentation patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients were detected by screening mammography (77.8 percent of cases versus 90.7 percent of controls; p = 0.010). Patients with implants were more likely to undergo an excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001), rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p < 0.001). Earlier staging in augmented patients approached but did not reach statistical significance (p = 0.073). Augmented patients had higher mastectomy rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type nor anatomic location affected method of diagnosis, stage, or treatment., Conclusions: Palpable detection of breast cancer is more likely at a smaller size in augmented patients, yet it is less likely on screening mammography than in controls. Augmentation breast cancer patients have a comparable disease stage and are more likely to undergo mastectomy rather than lumpectomy. Both silicone and saline implants, whether placed submuscularly or subglandularly, have comparable effects on breast imaging, biopsy modality, and surgical intervention., Clinical Question/level of Evidence: Therapeutic, III.

Despite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAm's. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA-BRCA data were used for replication. 1,214 aDNAm's were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAm's with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAm's identified, 650 are known to be involved in cancer, including ESR1 and beta-estradiol responsive genes. Expression of DNMT3A was positively associated with age. Two aDNAm's showed borderline significant associations with DNMT3A expression; KRR1 (OR 6.57, 95% CI: 2.51-17.23) and DHRS12 (OR 6.08, 95% CI: 2.33-15.86). A subset of aDNAm's co-localized within vulnerable regions for somatic mutations in cancers including breast cancer. Expression of C19orf48 was inversely and significantly correlated with its methylation level. In the TCGA dataset, 84% and 64% of the previously identified aDNAm's were correlated with age in both normal-adjacent and tumor breast tissues, with differential associations by histological subtype. Given the similarity of findings in the breast tissues of healthy women and breast tumors, aDNAm's may be one pathway for increased breast cancer risk with age., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Background: Acellular dermal matrix has enjoyed extensive use in primary and secondary alloplastic breast aesthetic and reconstructive surgery. The objective of this study was to examine clinical outcomes between available acellular dermal matrix products: DermACELL (LifeNet Health, Virginia Beach, Va.) and AlloDerm Ready To Use (LifeCell Corp., Branchburg, N.J.)., Methods: A retrospective chart review was performed on 58 consecutive patients (100 breasts) reconstructed with either DermACELL (n = 30 patients; 50 breasts) or AlloDerm Ready To Use (n = 28 patients; 50 breasts). The mastectomies were performed by three different breast surgeons. All reconstructions were performed by the same plastic surgeon (T.A.P.). Statistical analysis was performed by means of Fisher's exact test., Results: Differences in the average age, body mass index, percentage having neoadjuvant/adjuvant chemotherapy or breast irradiation, and numbers of therapeutic and prophylactic mastectomies between the two groups were not statistically significant (p < 0.05). Complications in both cohorts of patients were clinically recorded for 90 days after immediate reconstruction. When comparing outcomes, patients in the DermACELL group had a significantly lower incidence of "red breast syndrome" (0 percent versus 26 percent; p = 0.0001) and fewer days before drain removal (15.8 days versus 20.6 days; p = 0.017). No significant differences were seen in terms of seroma, hematoma, delayed healing, infection, flap necrosis, or explantation., Conclusion: Patients reconstructed with DermACELL as compared with AlloDerm Ready To Use have significantly decreased number of days to drain removal and red breast syndrome and equivalent rates of other complications, including seroma, infection, flap necrosis, and explantation., Clinical Question/level of Evidence: Therapeutic, III.

Background: Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer., Results: A 41-miRNA model distinguished breast cancer risk in the discovery study (accuracy of 83.3%), which was replicated in the independent study (accuracy = 63.4%, P=0.09). Among the 41 miRNA, 20 miRNAs were detectable in serum, and predicted breast cancer occurrence within 18 months of blood draw (accuracy 53%, P=0.06). These risk-related miRNAs were enriched for HER-2 and estrogen-dependent breast cancer signaling., Materials and Methods: MiRNAs were assessed in two cross-sectional studies of women without breast cancer and a nested case-control study of breast cancer. Using breast tissues, a multivariate analysis was used to model women with high and low breast cancer risk (based upon Gail risk model) in a discovery study of women without breast cancer (n=90), and applied to an independent replication study (n=71). The model was then assessed using serum samples from the nested case-control study (n=410)., Conclusions: Studying breast tissues of women without breast cancer revealed miRNAs correlated with breast cancer risk, which were then found to be altered in the serum of women who later developed breast cancer. These results serve as proof-of-principle that miRNAs in women without breast cancer may be useful for predicting breast cancer risk and/or as an adjunct for breast cancer early detection. The miRNAs identified herein may be involved in breast carcinogenic pathways because they were first identified in the breast tissues of healthy women.

Background: For years, the safety and effectiveness of autologous fat grafting (AFG) for breast reconstruction have been in question, with particular concern over fat necrosis, calcifications, cyst formation, and interfering with the detection of breast cancer. However, increasing evidence suggests that the complication rates and clinical results are generally acceptable to both clinicians and patients. The emerging challenge is the numerous AFG techniques and systems, where there are limited knowledge and data. The objective of this study was to conduct a literature review that focuses on the safety, effectiveness, and efficiency of various AFG techniques as applied to the breast., Methods: A PubMed search using terms related to AFG was performed over a 5-year period (April 1, 2010-April 30, 2015). Original articles focused on AFG to the breast, with outcomes on safety, effectiveness, and efficiency, were included., Results: Five hundred ninety-eight articles were identified with 36 articles included (n = 4306 patients). Satisfaction rates were high although the prevalence of complications was low-similar to previous findings. Seven studies reported average operating room time with an overall mean of 125 minutes (range: 40-210). The mean volume of fat harvested was 558 mL (range: 120-1299), and fat injected was 145 mL (range: 20-607). A positive association between injection volume and operating time was observed., Conclusions: This review validates previous findings on the safety and effectiveness of AFG to the breast and highlights its efficiency. The efficiency data available, although limited, suggest that there is an opportunity to achieve time and cost savings while not sacrificing safety and effectiveness., Competing Interests: Braden Leung, Mousam Parekh, and David Macarios are employees of Acelity. Courtney Coles and Matthew Gitlin received funding to conduct research. Scott Spear is a consultant to LifeCell/Acelity Corporation, Allergan, Establishment labs, Novadaq, and Endurance labs. The Article Processing Charge was paid for by Acelity.

Single nucleotide polymorphisms (SNPs) in one-carbon metabolism genes and lifestyle factors (alcohol drinking and breast folate) may be determinants of whole-genome methylation in the breast. DNA methylation profiling was performed using the Illumina Infinium HumanMethylation450 BeadChip in 81 normal breast tissues from women undergoing reduction mammoplasty and no history of cancer. ANCOVA, adjusting for age, race and BMI, was used to identify differentially-methylated (DM) CpGs. Gene expression, by the Affymetrix GeneChip Human Transcriptome Array 2.0, was correlated with DM. Biological networks of DM genes were assigned using Ingenuity Pathway Analysis. Fifty-seven CpG sites were DM in association with eight SNPs in FTHFD, MTHFD1, MTHFR, MTR, MTRR, and TYMS (P <5.0 x 10 -5 ); 56% of the DM CpGs were associated with FTHFD SNPs, including DM within FTHFD. Gene expression was negatively correlated with FTHFD methylation (r=-0.25, P=0.017). Four DM CpGs identified by SNPs in MTRR, MTHFR, and FTHFD were significantly associated with alcohol consumption and/or breast folate. The top biological network of DM CpGs was associated with Energy Production, Molecular Transportation, and Nucleic Acid Metabolism. This is the first comprehensive study of the association between SNPs in one-carbon metabolism genes and genome-wide DNA methylation in normal breast tissues. These SNPs, especially FTHFD, as well as alcohol intake and folate exposure, appear to affect DM in breast tissues of healthy women. The finding that SNPs in FTHFD and MTR are associated with their own methylation is novel and highlights a role for these SNPs as cis-methylation quantitative trait loci., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Postoperative nipple malposition can be an aesthetically devastating problem for patients and a formidable challenge for surgeons. Reduction mammoplasty often includes plans to elevate the nipple-areolar complex (NAC); however, overelevation should be avoided. Its management is complicated because of the limited amount of skin between the nipple and the sternal notch and the desire to avoid creating scars that lie above the nipple in the superior aspect of the breast. Although superior malposition of the NAC should and can be prevented, there are direct and indirect surgical techniques that can assist in repositioning the NAC to an acceptable location., (Copyright © 2016 Elsevier Inc. All rights reserved.)

p16(INK4a) is a tumor suppressor gene, frequently hypermethylated in breast cancer; this epigenetic silencing of p16(INK4a) occurs early in carcinogenesis. The risk factors and functional consequences of p16(INK4a) methylation are unknown. Alcohol consumption, a breast cancer risk factor, impedes folate metabolism and may thereby alter gene methylation since folate plays a pivotal role in DNA methylation. In a cross-sectional study of 138 women with no history of breast cancer who underwent reduction mammoplasty, we studied breast cancer risk factors, plasma and breast folate concentrations, variation in one-carbon metabolism genes, p16(INK4a) promoter methylation and P16 protein expression. Logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). p16(INK4a) methylation was negatively correlated with P16 expression (r = -0.28; P = 0.002). Alcohol consumption was associated with lower breast folate (P = 0.03), higher p16(INK4a) promoter methylation (P = 0.007) and less P16 expression (P = 0.002). Higher breast folate concentrations were associated with lower p16(INK4a) promoter methylation (P = 0.06). Genetic variation in MTRR (rs1801394) and MTHFD1 (rs1950902) was associated with higher p16 (INK4a) promoter methylation (OR = 2.66, 95% CI: 1.11-6.42 and OR = 2.72, 95% CI: 1.12-6.66, respectively), whereas variation in TYMS (rs502396) was associated with less P16 protein expression (OR = 0.22, 95% CI: 0.05-0.99). Given that this is the first study to indicate that alcohol consumption, breast folate and variation in one-carbon metabolism genes are associated with p16(INK4a) promoter methylation and P16 protein expression in healthy tissues; these findings require replication., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

Background: Allergan's Natrelle round silicone-filled breast implants were approved by the U.S. Food and Drug Administration in 2006 based on interim results from the Core Study; final 10-year study results are now available., Methods: Seven hundred fifteen subjects were implanted with smooth and Biocell textured Natrelle round silicone implants and attended clinic visits at 0 to 4 weeks, 6 months, 1 year, and annually through 10 years. Approximately one-third of subjects underwent magnetic resonance imaging at years 1, 3, 5, 7, and 9 to assess rupture., Results: Complication rates showed modest increases over the previously published 6-year rates. The Kaplan-Meier capsular contracture rate was 18.9 percent for augmentation, 28.7 percent for revision-augmentation, and 24.6 percent for reconstruction. Among augmentation subjects, capsular contracture was significantly lower (p = 0.023) for submuscular (15.7 percent) versus subglandular (26.3 percent) placement. The overall rupture rate in the magnetic resonance imaging cohort was 13.0 percent for subjects and 7.7 percent for implants. By the end of the study, 81.8 percent of augmentation subjects still had an original implant in place. Using a five-point scale, 94.2 percent of augmentation, 83.8 percent of revision-augmentation, and 90.7 percent of reconstruction subjects reported being satisfied or definitely satisfied with their implants. Significant improvement over baseline was also seen in overall breast satisfaction and satisfaction with breast size, shape, feel, and how well they matched., Conclusion: The 10-year data from the Natrelle Core Study, which can guide surgeons and patients in decision-making, demonstrate safety and high levels of patient satisfaction., Clinical Question/level of Evidence: Therapeutic, III.

Background: Although it is well established that reconstruction of the irradiated breast is associated with diminished cosmetic results and more frequent complications, little is known about the specific effects of radiation therapy on the reconstructive outcomes after nipple-sparing mastectomy., Methods: Patients who had nipple-sparing mastectomy and had either previous radiation therapy for breast-conservation therapy or postmastectomy radiation therapy were reviewed. Patient demographics, reconstructive details, and postoperative outcomes were analyzed. Patient photographs were used to evaluate aesthetic parameters. Fisher's exact and t tests were used for comparison of groups, with a value of p < 0.05 considered significant., Results: Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy (72.2 percent) or before postmastectomy radiation therapy (27.8 percent), with an average follow-up of 3 years. First-stage complications occurred in six patients (33.3 percent). Nipple position was classified as high-riding in 55.6 percent of patients. Average time to revision was 13.3 months. Most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and high-riding nipple (22.4 percent). Capsular contracture occurred more commonly in patients who needed postmastectomy radiation therapy compared with those who had previously undergone breast-conservation therapy (40 percent versus 7.8 percent). Maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent)., Conclusions: Nipple-sparing mastectomy and implant reconstruction should be approached cautiously in the setting of radiation therapy. When early complications are present, significant morbidity may occur. Late revision surgery is common in this subset of patients. Implant malposition and a high-riding nipple occur most frequently., Clinical Question/level of Evidence: Therapeutic, III.

Background: Tabbed tissue expanders have the potential benefit of less migration during the expansion process, which may allow for more predictable outcomes. Despite this theoretical benefit, no study has critically evaluated the proposed advantage as compared with traditional nontabbed expanders. Therefore, the authors photographically analyzed the migration and movement of tabbed and nontabbed expanders throughout the reconstructive process., Methods: The authors performed a retrospective review of patients who underwent two-stage expander-to-implant reconstruction from 2010 to 2012. Standardized frontal photographs were used for analysis. Adobe Photoshop was used to measure the relative movement of each patient's expander from insertion until immediately before implant exchange and after implant exchange., Results: Forty-four breasts were analyzed. Migration was reduced significantly in all four directions for both the tissue expander and permanent implant stages of reconstruction. Medial, lateral, superior, and inferior migration of the tissue expander in the tabbed cohort was reduced by 59.5 percent (p = 0.001), 48.3 percent (p = 0.004), 53.4 percent (p = 0.0005), and 73.4 percent (p < 0.0001), respectively, compared with the nontabbed cohort. Likewise, medial, lateral, superior, and inferior migration of the permanent implant in the tabbed cohort was reduced by 44.3 percent (p = 0.049), 73.7 percent (p < 0.0001), 67.7 percent (p = 0.0008), and 61.0 percent (p = 0.003), respectively., Conclusions: Two-stage implant reconstruction allows for precision in implant placement after an appropriately placed expander. Tabbed expanders appear to maintain better positioning on the chest wall compared with nontabbed expanders during the expansion process, and may allow for more precise mound creation with the permanent implant., Clinical Question/level of Evidence: Therapeutic, III.

Background: The current standard for breast augmentation involves placement of an implant. As an alternative, surgeons have been exploring breast augmentation with autologous tissue in the form of injectable fat., Objectives: The authors explore the efficacy and safety of lipoaugmentation of the breast, with specific interest in volume changes, fat retention, overall aesthetic improvement, and patient satisfaction., Methods: Direct measurements, 2- and 3-dimensional images, mammograms, and magnetic resonance imaging (MRI) were obtained preoperatively from 10 consecutive patients undergoing augmentation mammaplasty with autologous fat transfer. These measurements were repeated 1 year postoperatively. Postoperative photo imaging was conducted at 3-month intervals for 1 year. Efficacy was evaluated by determining the volume of fat retention 1 year after the procedure with 3-dimensional imaging, standard breast MRI volume measurements, and subjective aesthetic comparisons., Results: The average amount of fat injected was 236 cc (90-324; SD, 69.8) in the right breast and 250 cc (90-300; SD, 65.1) in the left. The mean volume change based on 3-dimensional imaging was 85.1 cc (36% retention) for the right breast and 98.1 cc (39.2% retention) for the left. The mean volume change based on MRI measurements was 30.0 cc (39.8% change) on the right and 29.3 cc (38.1% change) on the left. Blinded observers found substantial improvement in 1 patient (10%), moderate improvement in 5 patients (50%), and minimal to no improvement in 4 (40%). Overall patient satisfaction was high, as measured by the abbreviated BREAST-Q. Radiologic abnormalities and artifacts were common and required additional imaging., Conclusions: Objective breast enlargement in this study was modest but yielded disproportionately high subjective patient satisfaction reports., Level of Evidence: 2.

Background: Little data exist on the safety of elective breast surgery following breast conservation therapy., Objectives: The authors evaluate their experience performing reduction mammaplasties and mastopexies in previously irradiated breasts., Methods: A retrospective chart review was conducted of all reduction mammaplasties and mastopexies in previously irradiated breasts performed by the 2 senior authors (MYN and SLS) from 1995 to 2012 (n = 18). Patient records were analyzed for demographics, perioperative and postoperative details, and complications., Results: During the study period, 12 reduction mammaplasties and 6 mastopexies were performed on breasts previously treated with breast conservation therapy. The average study participant age was 49.5 years, and average body mass index was 29. Average preoperative bra cup size was D/DD. One patient was a former smoker; 17 were nonsmokers. Eleven of the 18 patients had been previously treated with chemotherapy; average time between radiation therapy and surgery was 2.5 years. Average specimen weight in the 12 reduction mammaplasties was 623 g. Twenty-two percent (n = 4) of patients experienced a total of 5 minor complications; none required a return to the operating room. One patient (6%) experienced a major complication resulting in approximately 50% loss of breast tissue, which was reconstructed with a latissimus dorsi musculocutaneous flap. Seventeen patients (94%) had successful outcomes with preoperative goals achieved., Conclusions: In the previously irradiated breast, reduction mammaplasty and mastopexy should be approached with extra caution, but the surgeries may still be safely and successfully performed., Level of Evidence: 4.

Background: Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia., Methods: One hundred thirty-five revision breast reconstructive procedures using acellular dermal matrix (AlloDerm) in 118 patients (154 breasts) over a 5-year period were reviewed. Most procedures were revisions or part of the second stage of previous mastectomy reconstructions; three were revisions after reconstruction of congenital chest wall deformities., Results: Fifty-seven revisions (37 percent) were for inferior fold malposition, followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for symmastia. The overall complication rate was 5 percent. Revisions with acellular dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most common complication was capsular contracture, occurring in five breasts (3.2 percent). There was one infection (0.6 percent), failure to lower the inframammary fold in one breast (0.6 percent), and one persistence of rippling (0.6 percent). The mean follow-up was 207 days., Conclusions: Acellular dermal matrix has proven to be a reliable tool for managing some of the most common and challenging problems in implant-based breast reconstruction. Although there are few published data on the success of more conventional solutions to fold malposition, lower pole support, and capsular contracture, the addition of acellular dermal matrix to buttress these repairs has been shown to provide a high likelihood of success with a low risk of complications.

Background: Nipple-sparing mastectomy is a controversial option for breast cancer treatment due to locoregional recurrence and distant metastasis. In addition to these oncologic factors, technical factors such as ideal incision type or reconstructive options are also debatable. This systematic review examines current trends with nipple-sparing mastectomy, including selection criteria, locoregional and distant metastasis rates, incision choice, and reconstructive options., Methods: Systematic electronic searches were performed in the PubMed and Ovid databases using search terms for studies reporting outcomes following nipple-sparing mastectomy and all forms of reconstruction. Studies between 1970 and 2013 were reviewed. Pooled descriptive statistics with separate analyses for incision type and reconstructive method were performed., Results: Forty-eight studies met inclusion criteria, yielding 6615 nipple-sparing mastectomies for analysis. The overall pooled complication rate was 22 percent, the nipple necrosis rate was 7 percent, the locoregional recurrence rate was 1.8 percent, and the distant metastasis rate was 2.2 percent. Comparing combined patient cohorts for two-stage expander to implant, one-stage direct to implant, and autologous reconstruction demonstrated overall complication rates of 52.8, 16.7, and 23.7 percent and nipple necrosis rates of 4.5, 4.1, and 17.3 percent, respectively. Incision types were divided into five categories: radial, periareolar/circumareolar, inframammary, mastopexy, and transareolar, with nipple necrosis rates of 8.83, 17.81, 9.09, 4.76, and 81.82 percent, respectively, Conclusions: Nipple-sparing mastectomy appears to be an oncologically safe option for properly selected patients, with low rates of locoregional and distant metastasis. Overall complication and nipple necrosis rates are affected by incision location and reconstruction method. Randomized controlled trials are warranted to determine best incision and reconstructive methods., Clinical Question/level of Evidence: Therapeutic, IV.

Introduction: For patients undergoing prosthetic breast reconstruction whose device was removed because of infection or exposure, there is no published information examining long-term outcomes. Despite initial failure, many patients want to pursue breast reconstruction., Methods: A retrospective review was performed of immediate prosthetic breast reconstruction failures during a 5-year period., Results: A total of 26 patients (29 breasts) were identified who failed primary prosthetic 2-stage reconstruction. On average, the device was removed 262 days from the initial expander placement. Of these breasts, 19 were removed for infection, 7 for exposure, and 3 for a combination of both. Of these 29 failures, secondary reconstruction was attempted in 20 (69%). Among secondary reconstructions, 13 were with a device and 7 with autologous tissue. Of the 13 (92.3%) secondary device reconstructions, 12 were successful.Those in whom secondary reconstruction was attempted were younger at initial reconstruction (48 vs 57 years; P = 0.038), had lower body mass indexes (BMIs) (26.0 vs 29.4; P = 0.27), and smaller breasts (650 vs 979 g; P = 0.23) than those who did not attempt secondary reconstruction.Of the nipple-sparing mastectomy patients, 100% underwent secondary reconstruction, whereas only 61% of skin-sparing mastectomy patients underwent secondary reconstruction (P = 0.14).For patients undergoing secondary reconstruction, those receiving a second device reconstruction had lower BMIs (24.7 vs 28.5; P = 0.18) and smaller breasts (489 vs 946 g; P = 0.08) than those with autologous reconstructions; 15% of secondary implant reconstructions underwent irradiation versus 43% of the secondary autologous reconstructions (P = 0.29)., Conclusions: After failed prosthetic breast reconstruction, a second attempt with an implant in properly selected patients has a high success rate (92.3%).

Background: Postoperative nipple malposition can be an aesthetically devastating problem for patients and a formidable challenge for surgeons. The authors' aim was to identify the common antecedent events leading to high-riding nipples, provide a classification system for these problems, and discuss management., Methods: A retrospective review of medical records was conducted for patients who presented to the senior surgeon (S.L.S.) for management of a postoperative, excessively high nipple-areola complex over an 8-year period from January of 2004 to March of 2012. Demographic information, medical histories, operative details, and office records were reviewed for each patient. The high nipple-areola complex was classified as mild, moderate, or severe depending on the distance from the superior breast border to the top of the nipple-areola complex in relation to the vertical breast height., Results: Twenty-five women met study criteria, with 41 breasts determined to have an excessively high nipple-areola complex. The average patient was aged 44.3 years and had undergone 2.5±1.3 operations before the development of a notably high nipple-areola complex, including nipple-sparing mastectomy (32 percent), augmentation/mastopexy (29 percent), augmentation (27 percent), mastopexy (10 percent), and skin-sparing mastectomy with nipple reconstruction (2 percent). Patients were classified as having mild (27 percent), moderate (56 percent), or severe (17 percent) nipple-areola complex displacement; surgical correction was attempted in 54 percent of cases., Conclusions: A high-riding nipple-areola complex can develop following aesthetic or reconstructive surgery. Although many patients may not need or choose correction, there are surgical options that may be helpful in improving the nipple-areola complex position.

Background: Although acellular dermal matrix materials have been in use for over a decade in primary and secondary breast reconstruction and in some cosmetic breast surgery, little has been published on the outcomes of these materials for cosmetic applications., Methods: A retrospective institutional review board-approved review was conducted of all patients who had a specific acellular dermal matrix, Strattice, used for cosmetic breast surgery performed by the senior author (S.L.S.). Patient demographics, indications, surgical findings, and postoperative course were collected and data analyzed using descriptive statistical tools., Results: Between 2008 and 2012, Strattice was used in 43 cosmetic breast operations (75 breasts) performed by the senior author (S.L.S.). Sixty-nine of the 75 breasts (92 percent) were revision operations. Indications included inferior pole support [39 breasts (52 percent)], fold malpositions [28 breasts (37 percent)], capsular contracture [25 breasts (33 percent)], and rippling/palpability [six breasts (8 percent)]. Three patients (six breasts) had Strattice placed during primary augmentation/mastopexy. Seventy-four of the 75 breasts (98.7 percent) had successfully achieved the indication for which the Strattice was placed; one breast (1.2 percent) had some degree of relapse. The global complication rate for all patients in this study is 5.3 percent-two breasts (2.7 percent) had postoperative malposition, one breast (1.2 percent) had bottoming out, and one breast (1.2 percent) developed an infection that resulted in temporary device explantation., Conclusions: The use of Strattice is safe and may be helpful in the management of certain situations in cosmetic breast surgery, including needed lower pole support, capsular contracture, rippling, and implant malposition., Clinical Question/level of Evidence: Therapeutic, IV.

The high-riding nipple-areola complex is a clinical problem that can be encountered following cosmetic and reconstructive breast surgery. Because of the desire to avoid scars on the superior aspect of the breast and the limited availability of superior breast skin, it can be technically challenging to place the nipple-areola complex in a lower position. Multiple surgical strategies have attempted to lower it, and each has its advantages and disadvantages. Reciprocal rotation flaps have been used by the authors with success. They describe the surgical technique and outcomes in five breasts. The medical records of all patients who had reciprocal rotation flaps for high-riding nipple-areola complexes performed by the senior author (S.L.S.) were reviewed. The institutional review board-approved review included preoperative history and examination, surgical findings, surgical technique, and postoperative course. Five reciprocal rotation flap procedures were performed on four patients between 2005 and 2012 for high-riding nipple-areola complexes. The high-riding nipple-areola complexes were all iatrogenic, following reconstruction for nipple-sparing mastectomy or mastopexy. All nipple-areola complexes were successfully lowered with an average follow-up duration of 2.1 years. One breast that had undergone previous radiation therapy had a nipple-areola complex flap that appeared ischemic; the patient underwent hyperbaric oxygen therapy and the flap fully survived. Reciprocal rotation flaps are an effective strategy for management of the high-riding nipple-areola complex and can be safely performed with thoughtful planning and careful surgical technique. This technique is riskier in the irradiated breast but may be facilitated with hyperbaric oxygen therapy.

We investigated insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 concentrations in histologically normal breast tissues and assessed their association with plasma concentrations, and breast cancer risk factors. IGF-1 and IGFBP-3 were assessed in plasma and breast tissues of 90 women with no history of any cancer and undergoing reduction mammoplasty. Pearson correlations and ANOVAs were used to describe plasma-breast associations and biomarker differences by breast cancer risk factors, respectively. Multivariable regression models were used to determine associations between risk factors, and breast IGF-1 and IGFBP-3. The mean age of the study sample was 37.3 years, 58 % were white, and generally these women were obese (mean BMI = 30.8 kg/m(2)). We observed no plasma-breast correlation for IGF-1, IGFBP-3, or IGF-1/IGFBP-3 (r = -0.08, r = 0.14, and r = 0.03, respectively; p-values >0.05). Through age- and BMI-adjusted analysis, BMI and years of oral contraceptive (OC) use were inversely associated with breast IGF-1 (p-values = 0.02 and 0.003, respectively) and age was associated with breast IGFBP-3 (p = 0.01), while breast IGF-1/IGFBP-3 was higher in blacks than whites (1.08 vs. 0.68, p = 0.04) and associated with age and BMI (p-values = 0.03 and 0.002, respectively). In multivariable-adjusted models, some breast cancer risk factors studied herein explained 24, 10, and 15 % of the variation in breast IGF-1, IGFBP-3, and IGF-1/IGFBP-3, respectively. While reasons for the lack of plasma-breast hormone correlations in these cancer-free women are unknown, several factors were shown to be associated with breast concentrations. The lack of correlation between blood and tissue IGF-1 and IGFBP-3 suggests that studies of breast cancer risk assessing blood IGF-1 and IGFBP-3 may have important limitations in understanding their role in breast carcinogenesis.

Prosthetic-based breast reconstruction commonly involves device placement in either a total submuscular pocket or a partial subpectoral position for just superior pole coverage, with various possible strategies for inferior pole coverage. Historically, the pectoralis major muscle is managed either by suturing the muscle to the inferior flap or with marionette sutures; alternatively, the device is placed under total muscle/fascia coverage (under the pectoralis major, plus the serratus anterior and rectus abdominis muscles or fascia). For many plastic surgeons, acellular dermal matrix is now used instead to function as a sling or "hammock" supporting the periprosthetic pocket and thus covering the inferior pole of the device, attached to the pectoralis major muscle above and to the inframammary fold below. In addition to its added soft-tissue support in the inferior pole, acellular dermal matrix may help to stabilize the pectoralis major muscle along its inferolateral margin, create a well-defined inframammary fold, provide the opportunity to significantly increase intraoperative fill volume of the tissue expander, and reduce the incidence or severity of significant or symptomatic capsular contracture, particularly in a patient whose breast has been treated with radiation. In addition to its indications in primary breast reconstruction, acellular dermal matrix has been increasingly used in secondary revision reconstruction cases. It can be used to buttress capsulorrhapy and capsulotomy sites and it can be used to replace periprosthetic capsule following capsulectomy. While clinical experience is accruing for these indications, acellular dermal matrix continues to be used in primary and secondary breast reconstruction.

Background: Blood adipokines are associated with breast cancer risk; however, blood-breast adipokine correlations and factors that explain variation in adipokines are unknown., Methods: Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations., Results: Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma-breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma-breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin., Conclusions: Although we report positive plasma-breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis., Impact: A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues., (2012 AACR)

Background: Late seromas surrounding breast implants are becoming an increasingly important issue in breast surgery. The authors report their experience with late seromas and describe their previous management options., Methods: A multicenter retrospective review of patients who developed late seromas (clinically presenting seromas without evidence of overt or documented infection more than 1 year after implant operation) was performed. Management, surgical technique, outcomes, complications, culture findings, and cytology results were recorded., Results: Between 2005 and 2010, 28 late seromas were identified in 25 patients. The average interval from the patient's last surgery to seroma onset was 4.7 years; 27 of 28 breasts (96 percent) had a Biocell textured device in place at the time of seroma development. The late seromas in the series were managed as follows: 15 (53.6 percent) by complete capsulectomy, seroma drainage, and new implant placement; three (10.7 percent) by seroma drainage and new implant placement but without capsulectomy; two (7.1 percent) by complete capsulectomy and seroma drainage but without implant replacement; five (17.9 percent) by only ultrasound-guided seroma drainage without the need for surgical intervention; and three (10.7 percent) by antibiotic therapy alone. All cultures and cytology studies were negative for malignancy or infection; 27 of 28 seromas (96 percent) were treated successfully by one of the described approaches., Conclusions: Biocell textured implants were more likely to be associated with late seromas than were smooth shell implants. The overwhelming majority of late seromas appear to be idiopathic, without clear evidence of infection or malignancy. A graduated approach, including several different management strategies, was used to successfully manage these patients., Clinical Question/level of Evidence: Therapeutic, IV.

Background: The authors compared the outcomes of two-stage, acellular dermal matrix (AlloDerm)-assisted prosthetic breast reconstruction including different timings of radiotherapy., Methods: A review of two-stage, AlloDerm-assisted, prosthetic breast reconstructions from 2004 to 2010 was performed. All data were recorded prospectively and the study population was stratified by the timing of radiotherapy. Complications were analyzed following first- and second-stage reconstruction. The Spear-Baker classification of capsular contracture was modified for irradiated devices. Reconstructive failure was defined as nonelective removal of a breast prosthesis., Results: : AlloDerm-assisted prosthetic reconstruction was performed in 289 women (428 breasts). After first-stage reconstruction, clinically significant capsular contracture rates (grade III/IV) were higher in the radiation therapy during expansion group and in the radiation therapy before mastectomy group compared with the no-radiation therapy group. Three hundred fifty-three breasts (85.9 percent) successfully underwent second-stage reconstruction, with a median follow-up of 15.2 months. Of those 353 breasts, clinically significant capsular contracture (grade III/IV) was highest in the radiation therapy during expansion group. More often than in the other groups, the radiation therapy during expansion group failed two-stage reconstruction and required flaps in addition or as replacement., Conclusions: In AlloDerm-assisted prosthetic breast reconstruction, irradiated devices demonstrated higher rates of clinically significant capsular contracture following the first stage. These rates declined considerably on completion of reconstruction, with prostheses irradiated during expansion still having the highest frequency of clinically significant capsular contracture. With the follow-up reported, irradiated devices failed breast reconstruction less frequently and required autologous tissue less often than has been historically reported without acellular dermal matrix., Clinical Question/level of Evidence: Therapeutic, III.

Background: Capsular contracture (CC) is the most common complication following primary breast augmentation and one of the most common causes of reoperation. Various studies have suggested certain risk factors, including incision choice., Objectives: The authors investigate a possible association between the three most common breast augmentation incisions (inframammary, periareolar, and transaxillary) and CC., Methods: The authors conducted a retrospective chart review of 197 primary breast augmentation patients treated between 2003 and 2009. Significant CC was determined to have occurred if the patient required reoperation for her CC. Patients were excluded if they underwent an augmentation/mastopexy, had previously undergone breast surgery, or received shaped silicone gel implants. CC rates were analyzed on a per-patient basis with Fisher's exact test and on a per-breast basis with the Rao-Scott chi-squared test., Results: One hundred eighty-three patients (336 augmented breasts) were included. Average patient age was 36.5 years. Mean follow-up was 392.6 days. Surgical complications included six breasts with CC (1.8%), three with hematoma (0.9%), and one with an infection (0.3%). Transaxillary incisions produced the highest incidence of contracture (6.4%), followed by periareolar (2.4%) and inframammary (0.5%). There was a statistically-significant difference in the incidence of CC among the three incision sites (P=.03). The increased rate seen with transaxillary incisions versus inframammary incisions was also statistically-significant. No significant association between implant fill material and contracture was found (P=.27)., Conclusions: The risk of CC is significantly higher with transaxillary incisions than with periareolar or inframammary incisions., Level of Evidence: 4.

Background: To address those patients who do not meet anatomical criteria for nipple-sparing mastectomy, the authors use a staged approach: (1) mastopexy or breast reduction, (2) nipple-sparing mastectomy through the mastopexy incisions after a minimum of 3 to 4 weeks, and (3) the final reconstruction., Methods: Fifteen patients underwent nipple-sparing mastectomy at Georgetown University Hospital between 2007 and 2010 after planned or unrelated mastopexy or reduction. An institutional review board-approved retrospective chart review recorded demographic information and outcomes such as skin necrosis and device failure., Results: Fifteen patients (24 breasts) underwent nipple-sparing mastectomy after mastopexy or reduction with an average follow-up of 13 months. The staged procedure was planned in 10 patients [19 breasts (79 percent)] and unplanned, or coincidental, in five [five breasts (21 percent)]. The mastectomy was prophylactic in 17 breasts (71 percent) and therapeutic in seven (29 percent). Four of the 24 operated breasts (17 percent) experienced a complication. Two patients [two breasts (8 percent)] developed skin flap necrosis. Two patients [three breasts (13 percent)] developed minimal partial nipple-areola complex necrosis. One patient [one breast (4 percent)] had an expander explanted for infection related to skin flap necrosis. Fourteen patients [23 breasts (96 percent)] successfully recovered following nipple-sparing mastectomy and prior mastopexy or reduction without residual effects of nipple-areola complex or skin flap necrosis., Conclusions: The authors are comfortable offering the staged approach to nipple-sparing mastectomy to patients with moderately large or ptotic breasts. It may not be suitable for the very large or ptotic breast., Clinical Question/level of Evidence: Therapeutic, IV.

Background: Nipple-sparing mastectomy remains controversial and its adoption has been slow because of oncologic and surgical concerns., Methods: A retrospective study evaluated all nipple-sparing mastectomies performed at a single institution for therapeutic or prophylactic indications for which records were available., Results: Between 1989 and 2010, 162 nipple-sparing mastectomies were performed in 101 women. Forty-nine (30 percent) were performed for therapeutic purposes on 48 patients. A subareolar biopsy specimen was taken in 39 of 49 breasts (80 percent); four (10 percent) revealed ductal carcinoma in situ, and the nipple or nipple-areola complex was later removed. Four of 49 breasts (8 percent) in the therapeutic group had ischemic complications involving the nipple-areola complex, one of which (2 percent) was excised. With a mean follow-up of 2 years 6 months (range, 5 months to 9 years 5 months), no patients developed cancer in the nipple-areola complex. The remaining 113 mastectomies (70 percent) were performed prophylactically on 80 patients. The subareolar tissue was biopsied in 80 breasts (71 percent). One biopsy revealed lobular carcinoma in situ; none had ductal carcinoma in situ or invasive cancer. Two nipple-areola complexes (1.8 percent) were ischemic and excised. With a mean follow-up of 3 years 7 months (range, 5 months to 20 years 6 months), no patients developed new primary cancers in the nipple-areola complex., Conclusions: Nipple-sparing mastectomy can be safe in properly selected patients. A subareolar biopsy can effectively identify nipple-areola complexes that may harbor cancerous cells. Ischemic complications resulting in nipple loss can be minimized, and long-term follow-up suggests that this technique deserves further investigation in properly selected patients., Clinical Question/level of Evidence: Therapeutic, IV.

Background: Anecdotal reports and one case-control study suggested an association, without evidence of causation, between breast implants and anaplastic lymphoma kinase-negative anaplastic large T-cell lymphoma (ALCL), a rare non-Hodgkin's lymphoma. This review summarizes the published evidence, including case reports and epidemiologic studies., Methods: A PubMed search limited to English language articles was conducted using the search terms "breast implant" and "lymphoma," "primary T-cell breast lymphoma," or "breast implant and ALCL" to identify all published cases of breast-associated ALCL., Results: A total of 18 publications were retrieved describing 27 cases of ALCL in breast implant recipients. Breast-associated ALCL occurred in women with and without implants. Approximately 78 percent of cases (21 of 27) were CD30 anaplastic lymphoma kinase-negative, with an indolent clinical course. Both saline- and silicone-filled devices were identified; however, implant style and surface texture were largely unreported. The tumor stage at diagnosis was I in 16 of 27, II or higher in seven of 27, or unreported in four of 27. No prospective epidemiologic study has linked implants and ALCL; however, a single case-control study in Dutch women reported increased odds of association between ALCL and implants, and an estimated frequency of one in 1 million women with and without breast implants., Conclusions: An association, without evidence of causation, was reported between breast implants and ALCL. Further study is required to confirm this association. Breast-associated ALCL occurred rarely in women with and without breast implants and had a primarily indolent clinical course, which may provoke a revision of the World Health Organization nomenclature for lymphoma; however, aggressive clinical behavior was also reported. The cases of ALCL were not confined to a specific type of implant., Clinical Question/level of Evidence: Risk, V.

Acellular dermal matrices (ADM) have generated interest for their possible applications in secondary revisions following prosthetic breast reconstruction. These materials can be effective in a variety of situations, including implant displacement, synmastia, capsular contracture, incisional support, and pocket conversion. ADM can also be placed in the setting of delayed breast reconstruction and to augment nipple projection. These biomaterials have demonstrated feasibility and success for many complex deformities. However, there is an associated learning curve that includes an understanding of proper technique and patient selection. The authors review their cumulative experience between 2004 and 2010 with ADM for the correction of secondary deformities following prosthetic breast reconstruction, focusing on the indications for repair, traditional management, and management with ADM.

Background: The goal of this consensus is to establish an algorithm for the management of patients who develop a late or delayed periprosthetic fluid collection. A work group of practicing plastic surgeons and device industry physicians met periodically by teleconference and discussed issues pertinent to the diagnosis and management of late periprosthetic fluid collections in patients with breast implants. Based on these meetings, treatment recommendations and a treatment algorithm were prepared in association with an editorial assistant., Method: The work group participants discussed optimal care approaches developed in their private practices and from evidence in the literature., Results: The consensus algorithm and treatment and management recommendations represent the consensus of the group., Conclusions: The group concluded that late periprosthetic fluid collection (arbitrarily defined as occurring ≥ 1 year after implant) is an infrequently reported occurrence (0.1 percent) after breast implant surgery and that, at a minimum, management should include clinically indicated ultrasound-guided aspiration of fluid, with appropriate cultures and cytologic testing. Further evaluation and additional treatment is recommended for recurrence of periprosthetic fluid collection after aspiration, or clinical suspicion of infection or neoplasia.

Background: The number of techniques available for nipple reconstruction underscores the notion that achieving an acceptable result remains a challenge. To better assess the value of a composite nipple graft in unilateral breast reconstruction, a study was performed to evaluate donor-site morbidity and patient satisfaction using a composite nipple graft for unilateral nipple reconstruction following mastectomy and reconstruction in radiated and nonradiated patients., Methods: A retrospective chart review of all patients who underwent composite nipple reconstruction between October of 1993 and February of 2010 was performed. Medical records were reviewed for outcomes and complications. Each patient was asked to complete a previously validated survey to rate color and projection of both nipples, sensation, and contractility of the donor nipple, and whether she would, in retrospect, have the procedure again., Results: Fifty-nine patients were identified who underwent nipple reconstruction using a composite nipple graft. Thirty-four patients (57.6 percent) responded to the survey. Four surveys were returned due to an invalid address. Average time to breast mound completion was 6 months. Average time to complete nipple reconstruction was 3.6 months after breast mound completion. Ninety-seven percent of the reconstructions were successful., Conclusions: Composite nipple reconstruction is a useful technique that should be considered in unilateral nipple reconstruction and should be especially considered in patients whose breast has been irradiated, for which flap reconstruction for the nipple can be riskier. Although it is not possible to use in all patients, no other technique provides a nipple reconstruction that can so closely match the contralateral side in color, texture, and overall appearance.

Background: Acellular dermal matrix has been increasingly accepted in prosthetic breast reconstruction. Observed benefits include improved control and support of implant position, better implant coverage, and the suggestion of a decreased capsular contracture rate. Based on this positive experience, it is not surprising that acellular dermal matrix would be applied to other challenging implant-related problems. This study investigates the use of acellular dermal matrix for correction or prevention of implant-associated breast deformities., Methods: Patients who underwent primary aesthetic breast surgery or secondary aesthetic or reconstructive breast surgery using acellular dermal matrix and implants between November of 2003 and October of 2009 were reviewed retrospectively. Patient demographics, indications for acellular dermal matrix, and acellular dermal matrix type and inset pattern were identified. Preoperative and postoperative photographs, success or failure of the procedure, complications, and need for related or unrelated revision surgery were recorded., Results: Fifty-two patients had acellular dermal matrix placed alongside 77 breast prostheses, with a mean follow-up of 8.6 months (range, 0.4 to 30.4 months). Indications included prevention of implant bottoming-out (n = 6), treatment of malposition (n = 32), rippling (n = 20), capsular contracture (n = 16), and skin flap deficiency (n = 16). Seventy-four breasts (96.1 percent) were managed successfully with acellular dermal matrix. Three failures consisted of one breast with bottoming-out following treatment of capsular contracture, one breast with major infection requiring device explantation, and one breast with recurrent rippling. There was a 9.1 percent total complication rate, consisting of three mild infections, one major infection necessitating explantation, one hematoma, and one seroma., Conclusion: Based on this experience in 77 breasts, acellular dermal matrix has shown promise in treating and preventing capsular contracture, rippling, implant malposition, and soft-tissue thinning.

The United States has seen significant shifts in the breast implant market over the past five decades. From the moratorium on silicone gel breast implants in 1992 to their approval in 2006, there have been many developments in their manufacturing and usage. Meanwhile, saline breast implants have remained somewhat unchanged, still offering a few distinct advantages but none of the technological innovation of the silicone gel models. In this article, the authors review the current state of silicone gel and saline implants, as well as the advantages and disadvantages of each. Much of the current data on complications of gel and saline implants are examined, as well as some practical implications associated with the use of each implant type.

To determine the hypermethylation status of the promoter regions of tumour suppressor genes in breast tissues from healthy women and identify the determinants of these epigenetic changes. Questionnaires and breast tissues were collected from healthy women without a history of cancer and undergoing reduction mammoplasty (N= 141). Methylation for p16(INK4), BRCA1, ERalpha and RAR-beta promoter regions from breast tissues were determined by methylation specific PCR. Associations were examined with chi-square and Fisher's exact test as well as logistic regression. All statistical tests were two-sided. p16(INK4), BRCA1, ERalpha and RAR-beta hypermethylation were identified in 31%, 17%, 9% and 0% of the women, respectively. Women with BRCA1 hypermethylation had an eight-fold increase in the risk of ERalpha hypermethylation (P= 0.007). p16(INK4) hypermethylation was present in 28% of African-Americans, but 65% in European-Americans (P= 0.02). There was an increased likelihood of p16(INK4) or BRCA1 hypermethylation for women with family history of cancer (OR 2.3; 95%CI: 1.05-4.85 and OR 5.0; 95%CI: 1.55-15.81, respectively). ERalpha hypermethylation was associated with family history of breast cancer (OR 6.6; 95%CI: 1.58-27.71). After stratification by race, p16(INK4) in European-Americans and BRCA1 hypermethylation in African-Americans were associated with family history of cancer (OR 3.8; 95%CI: 1.21-12.03 and OR 6.5; 95%CI: 1.33-31.32, respectively). Gene promoter hypermethylation was commonly found in healthy breast tissues from women without cancer, indicating that these events are frequent and early lesions. Race and family history of cancer increase the likelihood of these early events.

Background: In 2004, the senior author (S.L.S.) published an algorithm for the management of breast device infection and/or exposure. The purpose of this study was to build on the authors' prior experience by expanding the cohort of patients and to identify risk factors for failed breast device salvage and recurrent infection/exposure., Methods: A retrospective study was carried out on a single plastic surgeon's experience between 1993 and 2008. Patients with infected and/or exposed breast devices were classified into one of seven groups and salvage rates were calculated. Patient demographics and wound culture pathogens were analyzed as possible risk factors for device loss and recurrent infection/exposure., Results: Over a 15-year period, the senior author managed 69 patients with 87 events of breast device infection and/or exposure. The overall salvage rate was 64.4 percent. Failed device salvage was significantly associated with the presence of atypical pathogens, such as gram-negative rods, methicillin-resistant Staphylococcus aureus, and Candida parapsilosis. Recurrent device infection and/or exposure was significantly associated with a history of radiotherapy or the presence of S. aureus on wound culture., Conclusions: Salvage of the infected and/or exposed breast prosthesis remains a challenging yet viable option for a subset of patients. Relative contraindications include atypical pathogens on wound culture, such as gram-negative rods, methicillin-resistant S. aureus, and C. parapsilosis. Patients with a prior device infection and/or exposure and a history of either radiotherapy or S. aureus on wound culture should be monitored closely for signs of recurrence and managed cautiously in the setting of elective breast surgery.

Newborn screening for cystic fibrosis (CF) offers the opportunity for early medical and nutritional intervention that can lead to improved outcomes. Management of the asymptomatic infant diagnosed with CF through newborn screening, prenatal diagnosis, or sibling screening is different from treatment of the symptomatically diagnosed individual. The focus of management is on maintaining health by preventing nutritional and respiratory complications. The CF Foundation convened a committee to develop recommendations based on a systematic review of the evidence and expert opinion. These guidelines encompass monitoring and treatment recommendations for infants diagnosed with CF and are intended to help guide families, primary care providers, and specialty care centers in the care of infants with CF.

Background: Symmastia is a rare but challenging problem to correct. A number of techniques have been proposed, but each has drawbacks in terms of reliability, accuracy, and difficulty. A recently described technique to treat subpectoral symmastia is reported whereby a new pocket is created between the deep surface of the pectoralis major muscle and the anterior surface of the periprosthetic capsule, the boundaries of which are limited by the adherence between the capsule and overlying tissue. The "neosubpectoral" pocket is therefore not a "repair" of the excessively medialized symmastia pocket, but is a new pocket, limited at its perimeter by the patient's own tissues rather than by sutures or a patch., Methods: A precise neosubpectoral plane is developed between the pectoralis major and the anterior implant capsule wall, with dissection limited to creating only the space necessary for proper placement of the implant. The technical details of this procedure are described. A chart review was conducted of all patients who underwent symmastia correction using this technique since December of 2003 at Georgetown University Hospital in the practices of Steven Teitelbaum, M.D., and G. Patrick Maxwell, M.D., Results: A total of 23 patients underwent symmastia correction using the neosubpectoral technique. Several of these patients presented for recurrence after failed capsulorrhaphy. There has been no recurrence of symmastia to date in this study. The average follow-up was 22 months. One postoperative hematoma and one seroma occurred. One patient had uncorrected, underdiagnosed inferior malposition from an earlier procedure requiring revision., Conclusions: The neosubpectoral technique is a method for the correction of symmastia that may offer a more efficient, accurate, and effective solution in a single stage. It is an appealing concept that allows for a site change while maintaining the subpectoral position. This procedure is technically straightforward and may offer a reliable means of correcting many other forms of implant malposition and difficult reconstructions.