Reversal of epigenetic aging and immunosenescent trends in humans.

Epigenetic "clocks" can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age-related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (-2.5-year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from -1.6 year/year from 0-9 month to -6.5 year/year from 9-12 month. The GrimAge predictor of human morbidity and mortality showed a 2-year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.

Comparison of superior gluteal artery musculocutaneous and superior gluteal artery perforator flaps for microvascular breast reconstruction.

BACKGROUND: At the authors' institution, the superior gluteal artery musculocutaneous flap has been replaced by the superior gluteal artery perforator flap for autologous breast reconstruction. The authors present a head-to-head comparison of the two techniques. METHODS: A retrospective chart review of 102 gluteal flap transfers in 80 patients compared the two methods with regard to perioperative details, complications (especially anastomotic), and the number of secondary procedures required to achieve optimal outcome. Statistical analysis was carried out, and a value of p < 0.05 was considered significant. RESULTS: Seventy superior gluteal artery and 32 superior gluteal artery perforator flap procedures were performed over a period of 10 years. Patients in the superior gluteal artery perforator group tended to lose significantly less blood (375 cc versus 241 cc). There was no significant difference in the duration of surgery, hospital stay, or the overall complication rate. Even though the difference in the rate of anastomotic thrombosis (10 percent and 6 percent, respectively) was not statistically significant, patients in the superior gluteal artery group were prone to venous thrombosis, were more likely to require vein grafting, and had a higher rate of reoperation for anastomotic problems. There was no difference in the number of secondary operations. CONCLUSIONS: This report provides some evidence of the superiority of the superior gluteal artery perforator flap over the superior gluteal artery flap for breast reconstruction, particularly with regard to ease and reliability of the microvascular anastomosis. However, in the expert hands of its early proponents, the superior gluteal artery flap did remarkably well.

Risk factors for abdominal donor-site morbidity in free flap breast reconstruction.

BACKGROUND: The lower abdomen is the most popular donor site for autologous tissue breast reconstruction. Several studies have reported abdominal morbidity following pedicled and free flap reconstructions using this donor site, yet few studies have compared the various types of free flaps and investigated specific operative and patient-related factors that are associated with higher rates of abdominal complications. METHODS: The authors conducted a retrospective review of all free flap breast reconstructions performed at University of California Los Angeles Medical Center between July of 2002 and July of 2005. RESULTS: A total of 279 patients underwent 211 unilateral and 68 bilateral reconstructions, totaling 347 flaps. Eleven percent were free transverse rectus abdominis myocutaneous (TRAM) flaps, 52 percent were muscle-sparing free TRAM flaps, and 37 percent were deep inferior epigastric perforator (DIEP) flaps. Mean follow-up was 29.9 months. There were 30 total abdominal complications (10.9 percent of patients), including 17 rectus bulges and five hernias. Free TRAM reconstructions had a significantly higher rate of donor-site complications than did DIEP reconstructions. Bilateral flap harvests and obesity (body mass index >30) were significant risk factors for (1) any donor-site complication and (2) rectus bulge/hernia formation. There was no significant increase in donor-site complications associated with various prior abdominal operations. CONCLUSIONS: Donor-site complications are not uncommon, but paying careful attention to patient comorbidities when selecting an operative approach (bilateral versus unilateral, free TRAM versus DIEP, and so on) can minimize postoperative abdominal complications. Furthermore, the results corroborate the recent literature suggesting there is little functional difference in patients receiving muscle-sparing free TRAM versus DIEP reconstructions.

Late free-flap salvage with catheter-directed thrombolysis.

INTRODUCTION: Despite high success rates with free-tissue transfer, flap loss continues to be a devastating event. Flap salvage is often successful if vascular complications are recognized and treated early. However, delayed presentation of flap compromise is an ominous predictor of flap loss. Late free-flap salvage has been described with poor long-term results. Catheter-directed thrombolysis (CDT) has only been described in context with free-tissue transfer in a case of distal bypass salvage. OBJECTIVES: The authors examined the efficacy of highly selective CDT in late salvage of free-flaps with vascular compromise. METHODS: Two patients underwent highly selective CDT after delayed presentation (>5 days) of flap compromise. Patient 1 is a 59-year-old woman who underwent delayed breast reconstruction with a free TRAM flap and presented with arterial thrombosis 12 days postoperatively. Patient 2 is a 53-year-old man who underwent fibular osteocutaneous free-flap reconstruction of a floor of mouth defect who developed venous thrombosis 6 days postoperatively. Patient 2 underwent two attempted operative anastamotic revisions with thrombectomies and local thrombolysis prior to CDT. RESULTS: The average time of presentation was 9 days, with the average time to CDT being 9.5 days. Patient 1 had an arterial thrombosis, whereas Patient 2 had a venous thrombosis. Both patients underwent successful thrombolysis after super-selective angiograms. Continuous infusions of thrombolytic agents were used in both patients for approximately 24 h. Average length of stay postCDT was 7 days with no perioperative complications. Long-term follow-up demonstrated complete flap salvage with no soft tissue loss. CONCLUSION: Despite extremely delayed presentation, aggressive CDT was successful in both breast, and head and neck reconstructions with excellent long-term flap results. CDT appears to be a useful modality in managing difficult cases of free-flap salvage.

Complications after microvascular breast reconstruction: experience with 1195 flaps.

BACKGROUND: Reconstruction is an important adjunct to breast cancer management. This study evaluated the frequency of major and minor complications in the largest reported series of consecutive mastectomy patients treated with free tissue transfer for breast reconstruction. METHODS: All patients treated with microvascular breast reconstruction at the University of California, Los Angeles, Medical Center over an 11-year period were identified using a retrospective analysis. Frequency of complications was assessed. RESULTS: A total of 1195 breast reconstructions were performed in 952 patients. Transverse rectus abdominis musculocutaneous flaps were used in most cases (81.8 percent), whereas the superior gluteal musculocutaneous flap (10.1 percent) and other free flaps were used in the remaining patients. The overall complication rate was 27.9 percent and consisted primarily of minor complications (21.7 percent). Major complications were noted in 7.7 percent, including six total flap losses (0.5 percent). Obesity was a major predictor of complications. Smoking was not associated with increased rates of overall or microsurgical complications. Neoadjuvant chemotherapy was also an independent predictor of complications and was associated with wound-healing problems and fat necrosis. Prior abdominal surgery in transverse rectus abdominis musculocutaneous flap patients increased the risk of partial flap loss, fat necrosis, and donor-site complications. CONCLUSIONS: Microsurgical breast reconstruction is a safe and highly effective technique. Complications tend to be minor and do not affect postreconstruction adjuvant therapy. Obesity is a major predictor of flap and donor-site complications, and these patients should be appropriately counseled. Similarly, neoadjuvant preoperative chemotherapy and prior abdominal surgery increase the rates of minor complications.

Suction-assisted lipoplasty: physics, optimization, and clinical verification.

BACKGROUND: Although suction-assisted lipoplasty (SAL) has been clinically practiced for more than 25 years, comparatively little investigation into fundamental physics of the instrumentation used in the procedure has been conducted. Moreover, relatively little is known about the clinical impact or merit of the wide variety of instrumentation currently available. OBJECTIVE: In this study, we examined the physics related to the various components of instrumentation used in lipoplasty, and developed means to optimize performance based on quantified bench and clinical data. METHODS: The components used to construct a lipoplasty system (vacuum pump, suction tubing, suction canister, and suction cannula) were first evaluated using methods of bench experimentation. A selected set of components/parameters were then evaluated in a clinical setting, and the results were correlated to the bench data. The following design parameters were analyzed: for cannulas-shaft length, shaft internal diameter, port size/pattern, and venting; for tubing-length, internal diameter, and collapsibility; for canisters-volume, pull-down speed, gradation precision, and splash-related issues; and for vacuum pumps-vacuum level and flow rate. RESULTS: Each of the system components can have a significant impact on the overall performance of the system. A simple calculation is presented that can be used to quantify the relative "resistance" and, therefore, speed of any selected cannula or tube. Port area is shown to be an important aspect of cannula design and clinical performance. Clinical data are shown to correlate reasonably with bench data, which imparts credibility to the bench data and provides a platform from which to extrapolate other bench data to the clinical setting. CONCLUSIONS: With clinical objectives in mind, guidelines and recommendations are presented, based on the data we collected, to optimize a lipoplasty system with regard to choices of the vacuum pump, suction tubing, and canister. With the ideal system in place, the cannula becomes the only remaining variable. Cannula properties and performance were also studied and are discussed in detail.

Improving recipient vessel exposure during microvascular breast reconstruction.

Microvascular tissue transfer has become the gold standard for breast reconstruction. The primary drawback to these procedures is the technical expertise required for microsurgical anastomosis. This problem is compounded by the difficulties in the exposure of recipient vessels deep within the axilla. Previous techniques used for exposure of these vessels are difficult to setup, provide less than optimal exposure, and have been associated with brachial plexus injuries. The authors retrospectively review their experience using the pediatric OMNI retractor for exposure of recipient vessels during microvascular breast reconstruction. Patient demographics, flap choice, recipient vessels, the incidence of neuropraxia/brachial plexopathy, and microvascular complications were analyzed. Patients in whom more traditional methods of vessel exposure were used (ie, Gelpi retractors, arm positioning, fish hooks; 517 reconstructions in 392 patients) were compared with patients in whom vessel exposure was performed using the pediatric OMNI retractor (699 reconstructions in 571 patients). No differences were noted in comorbid conditions or the incidence of microvascular complications. However, the use of the pediatric OMNI was associated with a significant reduction in operative time in unilateral reconstructions (6:23 +/- 0.05 h vs 7:48 +/- 0.05 h; P <0.01) and decreased incidence of brachial plexus injury (0.17% vs 3.3%; P <0.01). The authors think the decreased neuropraxia rate is the result of better exposure afforded by the pediatric OMNI retractor, which improves exposure and eliminates the need for excessive arm abduction or awkward positioning during the dissection and anastomosis of axillary recipient vessels.

Reconstruction of composite through-and-through mandibular defects with a double-skin paddle fibular osteocutaneous flap.

Microsurgical reconstruction of composite through-and-through defects of the oral cavity involving mucosa, bone, and external skin has often required two free flaps or double-skin paddle scapular or radial forearm flaps for successful functional and aesthetic outcomes. A safe, reliable technique using a double-skin paddle fibular osteocutaneous flap to restore the intraoral lining, mandibular bone, and external skin is described. A large elliptical or rectangular skin paddle is designed 90 degrees to the longitudinal axis of the fibula, over the junction of the middle and distal thirds of the lower leg, based only on the posterolateral septocutaneous perforators. This skin flap can be draped anteriorly and posteriorly over the fibular bone to reconstruct both the intraoral defect and the external skin defect. The area between the two skin islands of the intraoral flap and the external flap is deepithelialized and left as a dermal bridge between the two skin islands, as opposed to the creation of two separate vertical skin paddles, each based on a septocutaneous perforator. The transverse dimension of the flap can be as great as 14 cm, extending to within 1 to 2 cm of the tibial crest anteriorly and as far as the midline posteriorly, and with a length of up to 26 cm, this flap should be more than sufficient for reconstruction of most through-and-through defects. This technique has allowed the successful reconstruction of large composite defects, with missing intraoral lining, mandibular bone, and external skin, for 16 patients, with 100 percent survival of both skin islands in all cases and without the development of any orocutaneous fistulae.

Alternative venous outflow vessels in microvascular breast reconstruction.

The lack of adequate recipient vessels often complicates microvascular breast reconstruction in patients who have previously undergone mastectomy and irradiation. In addition, significant size mismatch, particularly in the outflow veins, is an important contributor to vessel thrombosis and flap failure. The purpose of this study was to review the authors' experience with alternative venous outflow vessels for microvascular breast reconstruction. In a retrospective analysis of 1278 microvascular breast reconstructions performed over a 10-year period, the authors identified all patients in whom the external jugular or cephalic veins were used as the outflow vessels. Patient demographics, flap choice, the reasons for the use of alternative venous drainage vessels, and the incidence of microsurgical complications were analyzed. The external jugular was used in 23 flaps performed in procedures with 22 patients. The superior gluteal and transverse rectus abdominis musculocutaneous (TRAM) flaps were used in the majority of the cases in which the external jugular vein was used (72 percent gluteal, 20 percent TRAM flap). The need for alternative venous outflow vessels was usually due to a significant vessel size mismatch between the superior gluteal and internal mammary veins (74 percent). For three of the external jugular vein flaps (13 percent), the vein was used for salvage after the primary draining vein thrombosed, and two of three flaps in these cases were eventually salvaged. In three patients, the external jugular vein thrombosed, resulting in two flap losses, while the third was salvaged using the cephalic vein. A total of two flaps were lost in the external jugular vein group. The cephalic vein was used in 11 flaps (TRAM, 64.3 percent; superior gluteal, 35.7 percent) performed in 11 patients. In five patients (54.5 percent), the cephalic vein was used to salvage a flap after the primary draining vein thrombosed; the procedure was successful in four cases. In three patients, the cephalic vein thrombosed, resulting in two flap losses. One patient suffered a thrombosis after the cephalic vein was used to salvage a flap in which the external jugular vein was initially used, leading to flap loss, while a second patient experienced cephalic vein thrombosis on postoperative day 7 while carrying a heavy package. There was only one minor complication attributable to the harvest of the external jugular or cephalic vein (small neck hematoma that was aspirated), and the resultant scars were excellent. The external jugular and cephalic veins are important ancillary veins available for microvascular breast reconstruction. The dissection of these vessels is straightforward, and their use is well tolerated and highly successful.

Surgical treatment of breast cancer in previously augmented patients.

The incidence of breast cancer is increasing each year. Concomitantly, cosmetic breast augmentation has become the second most often performed cosmetic surgical procedure. As the augmented patient population ages, an increasing number of breast cancer cases among previously augmented women can be anticipated. The surgical treatment of these patients is controversial, with several questions remaining unanswered. Is breast conservation therapy feasible in this patient population and can these patients retain their implants? A retrospective review of all breast cancer patients with a history of previous augmentation mammaplasty who were treated at the Revlon/UCLA Breast Center between 1991 and 2001 was performed. During the study period, 58 patients were treated. Thirty patients (52 percent) were treated with a modified radical mastectomy with implant removal. Twenty-eight patients (48 percent) underwent breast conservation therapy, which consisted of lumpectomy, axillary lymph node dissection, and radiotherapy. Twenty-two of the patients who underwent breast conservation therapy initially retained their implants. Eleven of those 22 patients (50 percent) ultimately required completion mastectomies with implant removal because of implant complications (two patients), local recurrences (five patients), or the inability to obtain negative margins (four patients). Nine additional patients experienced complications resulting from their implants, including contracture, erosion, pain, and rupture. The data illustrate that breast conservation therapy with maintenance of the implant is not ideal for the majority of augmented patients. Breast conservation therapy with explantation and mastopexy might be appropriate for rare patients with large volumes of native breast tissue. Mastectomy with immediate reconstruction might be a more suitable choice for these patients.