Familial and racial determinants of tumour suppressor genes promoter hypermethylation in breast tissues from healthy women.

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.

Acellular dermis-assisted breast reconstruction.

BACKGROUND: In 2004, the authors reported their findings with placement of tissue expanders for breast reconstruction in the partial submuscular position, the equivalent of the "dual-plane" technique for breast augmentation. Limitations with subpectoral expander placement include difficulty controlling the lower pole of the pocket during expansion, unprotected device coverage by a thin inferior mastectomy flap, possible effacement of the inframammary fold, and limited control over the superior migration of the pectoralis major muscle. This study aimed to examine the safety and efficacy of an acellular dermal sling in providing inferolateral support to the device during immediate breast reconstruction and expansion. METHODS: This study prospectively investigated 58 breasts of 43 consecutive women who underwent immediate breast reconstruction with tissue expanders and acellular dermis. After completion of adjuvant therapy and expansion, the devices were exchanged for implants. The patients were tracked through January, 2007. The study parameters included demographic information, oncologic data, complications, and aesthetic outcomes. RESULTS: The mean time required to complete reconstruction was 8.6 months. The overall complication rate after expander/acellular dermis placement was 12%, whereas the complication rate after exchange to implants was 2.2%. The aesthetic outcome for reconstructed breasts did not differ significantly from that for the control subjects who had no surgery. CONCLUSIONS: Acellular dermis appears to be a useful adjunct in immediate prosthetic breast reconstruction. Acellular dermis-assisted breast reconstruction has a low complication rate, helps to reconstruct an aesthetically pleasing breast, and facilitates expeditious completion of the reconstruction.

Improvements in cardiovascular risk profile with large-volume liposuction: a pilot study.

In this study, the authors investigated the physiologic effects of the altered body composition that results from surgical removal of large amounts of subcutaneous adipose tissue. Fourteen women with body mass indexes of greater than > 27 kg/m2 underwent measurements of fasting plasma insulin, triglycerides, cholesterol, body composition by dual-energy x-ray absorptiometry (DXA), resting energy expenditure, and blood pressure before and after undergoing large-volume ultrasound-assisted liposuction. There were no significant intraoperative complications. Body weight had decreased by 5.1 kg (p < 0.0001) by 6 weeks after liposuction, with an additional 1.3-kg weight loss (p < 0.05) observed between 6 weeks and 4 months after surgery, for a total weight loss of 6.5 kg (p < 0.00006). Body mass index decreased from (mean +/- SEM) 28.8 +/- 2.3 to 26.8 +/- 1.5 kg/m2 (p < 0.0001). This change in body weight was primarily the result of decreases in body fat mass: as assessed by DXA, lean body mass did not change (43.8 +/- 3.1 kg to 43.4 +/- 3.6 kg, p = 0.80), whereas DXA total body fat mass decreased from 35.7 +/- 6.3 to 30.1 +/- 6.5 kg (p < 0.0001). There were significant decreases in fasting plasma insulin levels (14.9 +/- 6.5 mIU/ml before liposuction versus 7.2 +/- 3.2 mIU/ml 4 months after liposuction, p < 0.007), and systolic blood pressure (132.1 +/- 7.2 versus 120.5 +/- 7.8 mmHg, p < 0.0002). Total cholesterol, high-density lipoprotein cholesterol, plasma triglycerides, and resting energy expenditure values were not significantly altered after liposuction. In conclusion, over a 4-month period, large-volume liposuction decreased weight, body fat mass, systolic blood pressure, and fasting insulin levels without detrimental effects on lean body mass, bone mass, resting energy expenditure, or lipid profiles. Should these improvements be maintained over time, liposuction may prove to be a valuable tool for reducing the comorbid conditions associated with obesity.

Alternative filler materials and new implant designs: what's available and what's on the horizon?

Despite ample evidence that silicone gel-filled implants do not cause systemic illness, they are still not available in the United States for widespread use. At this point, saline-filled implants are widely available for use, and assuming favorable outcomes of the relevant silicone studies, some forms of silicone gel-filled implants could be approved by the FDA and be available as soon as 2003. Other products under preliminary consideration by the FDA for eventual studies include the 150 series and the cohesive silicone gel-filled 410 series by McGhan, and the NovaGold implant by NovaMed. Assuming favorable study results, one or more could be approved by the FDA by the year 2004. Any products not yet submitted to the FDA for review of study designs by this time are not likely to be available in the United States in the next 4 or 5 years.

Breast augmentation with reduced-height anatomic implants: the pros and cons.

The reduced-height anatomic saline-filled implant has certain advantages. It has a distinct footprint and profile that allows the creation of a breast with relatively exaggerated width and abbreviated height. This creation suits certain anatomic situations and often is preferred by women seeking a more natural-looking augmentation, without excessive upper pole fullness. The use of any anatomic design implant requires some dimensional planning and more precise pocket dissection. Although the risk for rotational deformities could be expected to be increased, clinically significant rotational deformities have not been a major problem.

Postmastectomy reconstruction of the previously augmented breast: diagnosis, staging, methodology, and outcome.

Although many of the health and safety issues associated with breast augmentation have been thoroughly discussed over the past decade, the literature is remarkably silent regarding postmastectomy reconstruction of the previously augmented breast. A retrospective review of the senior author's reconstructive practice was performed for the years 1983 through March of 1999, revealing 21 women who underwent postmastectomy breast reconstruction after previous breast augmentation. For purposes of measuring aesthetic results, these 21 patients were matched to a carefully selected control group of 15 patients. They were also compared with other, larger populations, including 777 of the senior author's other breast reconstructions, the breast cancer registry at the Lombardi Cancer Center in Washington, D.C., and several large, published epidemiologic studies. The interval between the previous augmentation and the diagnosis of breast cancer ranged from 9 months to 18 years, with a mean of 9.3 years. None of the previous augmentation implants was ruptured at the time of mastectomy. Of the nine patients with previous subpectoral augmentation, cancer was detected mammographically in five (56 percent), whereas of the 12 patients with previous subglandular augmentation, cancer was first detected mammographically in only three (25 percent). This difference was not statistically significant (p = 0.2). Overall, eight of the study patients' tumors (38 percent) were first detected mammographically, which is similar to other published reports of breast cancer patients in the general population. Seventy-one percent of the 21 study patients were node-negative, which also compares favorably with other published series. Sixteen of the women with previous augmentation (76 percent) had purely prosthetic reconstructions. Flaps were used in the other five reconstructions (23 percent): three latissimus dorsi flaps (14 percent) and two transverse rectus abdominis musculocutaneous flaps (9 percent). All five flaps were used in patients who had undergone radiation therapy. Throughout the senior author's entire reconstructive practice history, transverse rectus abdominis musculocutaneous flaps were more frequently used [282 of 777 nonaugmented reconstructions (36 percent)], whereas latissimus dorsi flaps were less frequently used [17 of 777 nonaugmented reconstructions (2.2 percent)] (p < 0.001). The cosmetic results of the breast reconstructions in the previously augmented study group were generally good-to-excellent, with a mean score by blinded observers of 3.35 of a possible 4.0. These results were comparable to or better than those in the matched controls, who scored a mean of 3.0.

Breast reconstruction with implants and expanders.

Breast reconstruction with expanders and implants provides an excellent option in the properly selected patient. Techniques for reconstruction have evolved significantly over the past 30 years with the development of more sophisticated devices and improvement in surgical procedures. Several options exist, each with its own advantages and disadvantages. Two-stage breast reconstruction using a textured device with an anatomic shape and integrated valve seems to provide the most consistent and reproducible results in most patients. Those patients with small, minimally ptotic breasts may be candidates for either single-stage implant reconstruction or reconstruction with an adjustable device. Advantages of expander and implant reconstruction over other techniques include relative ease of the procedure; no distant donor-site morbidity; use of tissue of similar color, texture, and sensation; reduced operative time; and more rapid postoperative recovery.

Improvements in cardiovascular risk profile after large-volume lipoplasty: a 1-year follow-up study.

BACKGROUND: Large-volume lipoplasty changes body composition during a single surgical intervention by selectively decreasing subcutaneous adipose tissue. Positive health benefits, previously reported for a cohort of 14 women at 4 months after surgery, include significant decreases in weight, systolic blood pressure, and fasting insulin levels. OBJECTIVE: In the present study, we sought to determine whether the benefits of altering body composition by large-volume liposuction observed at 4 months are sustained over longer periods of time. METHODS: Subjects were seen for an additional follow-up visit approximately 1 year (range 10 to 21 months) after surgery. Fasting insulin levels were measured in the 8 patients who had preoperative fasting insulin levels higher than 12 muU/mL. Weight, systolic and diastolic blood pressure, heart rate, and body circumferences were measured in all 14 subjects. RESULTS: Compared with data obtained before surgery and 4 months after surgery, results at 10 to 21 months after lipoplasty showed that the improvements in body weight, systolic blood pressure, and fasting insulin levels observed 4 months after the procedure had been maintained. CONCLUSIONS: Should these results be confirmed in larger studies, lipoplasty may prove to be a valuable tool for reducing some of the co-morbid conditions associated with obesity. (Aesthetic Surg J 2001;21:527-531.).

Evaluation of abdominal sensibility after TRAM flap breast reconstruction.

One commonly expressed concern regarding transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction surgery is the return of sensation to the abdomen. Although many studies have focused on abdominal wall muscle incompetence or herniation, there is limited literature discussing postoperative abdominal sensation. The purpose of this study was to assess abdominal sensation a minimum of 1 year after pedicled TRAM flap surgery for breast reconstruction. Twenty-five female patients who underwent TRAM flap breast reconstruction a minimum of 1 year before the study were compared with 10 female volunteer controls. Subject and control abdomens were specifically divided into 12 zones, then assessed for superficial touch, superficial pain, temperature, and vibration using various techniques. Fischer's exact test was used for analysis with the p value set at p = 0.05. The degree to which superficial touch was affected was then tested using Semmes-Weinstein monofilaments. Student's t test was used for analysis with the p value set at p = 0.05. For all four sensory modalities, subjects were found to have decreased sensation in zones 5 and 8, the supraumbilical and infraumbilical regions. This was statistically significant. When assessed with Semmes-Weinstein monofilaments, the sensation of the subjects' abdomens was significantly decreased compared with controls. Significance was found in all zones. This study clearly demonstrates that there is a significant and persistent reduction in abdominal sensibility following TRAM flap surgery. The distribution of the deficits is consistent and involves the midline supraumbilical and infraumbilical regions. The TRAM flap has become the procedure of choice for postmastectomy autogenous breast reconstruction. It provides the plastic surgeon with a relatively safe, reliable, and aesthetically pleasing method of breast reconstruction. Since its inception, the TRAM flap and its abdominal closure have undergone numerous modifications designed to minimize donor-site morbidity and create a natural-looking breast. In addition to creating an aesthetically pleasing breast, the TRAM flap has the potential advantage of postoperative improvement in abdominal contour.

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty.

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.

Staged breast reconstruction with saline-filled implants in the irradiated breast: recent trends and therapeutic implications.

A retrospective review was performed of one surgeon's experience with 40 consecutive patients who had undergone two-stage saline-filled implant breast reconstruction and radiation during the period from 1990 through 1997. A randomly selected group of 40 other two-stage saline-filled implant breast reconstructions from the same surgeon and time period served as controls. This review was undertaken because of the absence of specific information on the outcome of staged saline implant reconstructions in the radiated breast. Previously published reports on silicone gel implants and radiation have been contradictory. At the same time, the criteria for the use of radiation in the treatment of breast cancer have been expanded and the numbers of reconstruction patients who have been radiated are increasing dramatically. For example, in a 1985 report on immediate breast reconstruction, only 1 of 185 patients over a 6-year period underwent adjuvant radiation therapy, whereas in this review, there were 40 radiated breasts with saline-filled implants, 19 of which received adjuvant radiation therapy during their expansion. The study parameters included patient age, breast cup size, implant size, length of follow-up, number of procedures, coincident flap operations, Baker classification, complications, opposite breast procedures, pathologic stage, indications for and details about the radiation, and outcomes. The use of radiation in this review of reconstructed breasts can logically be divided into four groups: previous lumpectomy and radiation (n = 7), mastectomy and radiation before reconstruction (n = 9), mastectomy and adjuvant radiation during reconstruction/expansion (n = 19), and radiation after reconstruction (n = 5). The largest and most rapidly growing group of patients is of those receiving postmastectomy adjuvant radiation therapy. A total of 47.5 percent (19 of 40) of radiated breasts with saline implants ultimately needed the addition of, or replacement by, a flap. Ten percent of a control group with nonradiated saline implant reconstructions also had flaps, none as replacements. Fifty percent or more of both the radiated and control groups had contralateral surgery. Complications were far more common in the radiated group; for example, there were 32.5 percent capsular contractures compared with none in the control group. The control nonradiated implant-only group and the flap plus implant radiated group did well cosmetically. The radiated implant-only group was judged the worst. The increasing use of radiation after mastectomy has important implications for breast reconstruction. The possibility for radiation should be thoroughly investigated and anticipated preoperatively before immediate breast reconstruction. Patients with invasive disease, particularly with large tumors or palpable axillary lymph nodes, are especially likely to be encouraged to undergo postmastectomy radiation therapy. The indications for adjuvant radiation therapy have included four or more positive axillary lymph nodes, tumors 4 cm (or more) in diameter, and tumors at or near the margin of resection. More recently, some centers are recommending adjuvant radiation therapy for patients with as few as one positive lymph node or even in situ carcinoma close to the resection margin. The use of latissimus dorsi flaps after radiation has proven to be an excellent solution to postradiation tissue contracture, which can occur during breast expander reconstruction. The use of the latissimus flap electively with skin-sparing mastectomy preradiation is probably unwise, unless postmastectomy radiation is unlikely. Skin-sparing mastectomy with a latissimus flap thus should be preserved for patients unlikely to undergo adjuvant radiation therapy. Purely autologous reconstruction such as a TRAM flap is another option for these patients, either before or after radiation therapy.

Experience with reduction mammaplasty following breast conservation surgery and radiation therapy.

Little is known about the outcome of breast reduction in the previously radiated breast. With the increased popularity of breast conservation in the management of breast cancer, it is inevitable that more women with breast cancer who have had a breast radiated will be seeking breast reduction. Although it would be expected that reduction of the radiated breast would be more challenging and would yield less-pleasing results, it has been unclear whether reduction in the radiated breast could be safely performed without interfering with mammography and cancer surveillance. Our experience using different techniques in three patients demonstrates that such reductions can be effectively and safely done if certain principles are followed. Pedicles should be designed to be broader and shorter than usual, and breast flaps should be undermined or elevated either minimally or not at all.

Breast reconstruction in a male with a transverse rectus abdominis flap.

The TRAM flap may be the best choice in male breast reconstruction not just because it can replace the missing skin and fat but also because it may be a source of hair-bearing skin similar to the native breast skin.