Sean Boutros

Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres.

&NA; The present investigation evaluates the effects of longterm, local delivery of insulin, insulin‐like growth factor‐1 (IGF‐1), and basic fibroblast growth factor (bFGF) on fatgraft survival using a poly (lactic‐co‐glycolic‐acid)‐polyethylene glycol (PLGA/PEG) microsphere delivery system. Twelve‐micrometer PLGA/PEG microspheres incorporated separately with insulin, IGF‐1, and bFGF were manufactured using a double‐emulsion solvent‐extraction technique. Inguinal fat from Sprague Dawley rats was harvested, diced, washed, and mixed with (1) insulin microspheres, (2) insulin‐like growth factor‐1 microspheres, (3) basic fibroblast growth factor microspheres, (4) a combination of the insulin and IGF‐1 microspheres, and (5) a combination of insulin, IGF‐1, and bFGF microspheres. The treated fat grafts were implanted autologously into subdermal pockets in six animals for each group. Animals receiving untreated fat grafts and fat grafts treated with blank microspheres constituted two external control groups (six animals per external control group). At 12 weeks, all fat‐graft groups were compared on the basis of weight maintenance and a histomorphometric analysis of adipocyte area percentage, indices of volume retention and cell composition, respectively. Weight maintenance was defined as the final graft weight as a percent of the implanted graft weight. All growth factor treatments significantly increased fat‐graft weight maintenance objectively, and volume maintenance grossly, in comparison with the untreated and blank microsphere‐treated controls. Treatment with insulin and IGF‐1, alone or in combination, was found to increase the adipocyte area percentage in comparison with fat grafts treated with bFGF alone or in combination with other growth factors. In conclusion, the findings of this study indicate that long‐term, local delivery of growth factors with PLGA/PEG microspheres has the potential to increase fat‐graft survival rates. Further, the type of growth factor delivered may influence the cellular/stromal composition of the grafted tissue. (Plast. Reconstr. Surg. 105: 1712, 2000.)

De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: A novel concept and capability

&NA; This study was undertaken to characterize the duration of long‐term growth factor delivery by poly(lactic‐co‐glycolicacid)‐polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long‐term delivery of insulin and insulin‐like growth factor‐1 (IGF‐1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF‐1, separately, were produced by a double‐emulsion solvent‐extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin‐containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF‐1, insulin + IGF‐1, and blank microspheres) (n = 4). Insulin and IGF‐1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4‐week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF‐1, and insulin + IGF‐1 microspheres. Such islands were not seen in the blank micro sphere group. Hematoxylin and eosin‐stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil‐Red‐O stained sections demonstrated that these cells contained lipid. Computer‐aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of “ectopic” adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long‐term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long‐term local insulin and IGF‐1 to induce adipogenic differentiation to mature lipid‐containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks. (Plast. Reconstr. Surg. 105: 1721, 2000.)

The tear trough and lid/cheek junction: anatomy and implications for surgical correction.

Background: The tear trough and the lid/cheek junction become more visible with age. These landmarks are adjacent, forming in some patients a continuous indentation or groove below the infraorbital rim. Numerous, often conflicting procedures have been described to improve the appearance of the region. The purpose of this study was to evaluate the anatomy underlying the tear trough and the lid/cheek junction and to evaluate the procedures designed to correct them. Methods: Twelve fresh cadaver lower lid and midface dissections were performed (six heads). The orbital regions were dissected in layers, and medical photography was performed. Results: In the subcutaneous plane, the tear trough and lid/cheek junction overlie the junction of the palpebral and orbital portions of the orbicularis oculi muscle and the cephalic border of the malar fat pad. In the submuscular plane, these landmarks differ. Along the tear trough, the orbicularis muscle is attached directly to the bone. Along the lid/cheek junction, the attachment is ligamentous by means of the orbicularis retaining ligament. Conclusions: The tear trough and lid/cheek junction are primarily explained by superficial (subcutaneous) anatomical features. Atrophy of skin and fat is the most likely explanation for age-related visibility of these landmarks. “Descent” of this region with age is unlikely (the structures are fixed to bone). Bulging orbital fat accentuates these landmarks. Interventions must extend significantly below the infraorbital rim. Fat or synthetic filler may be best placed in the intraorbicularis plane (tear trough) and in the suborbicularis plane (lid/cheek junction).

Clinical and scientific considerations in leech therapy for the management of acute venous congestion: An updated review

Any surgical intervention that involves the manipulation of veins, large or small, carries the risk of acute venous congestion. Venous congestion is the product of an imbalance between arterial inflow and venous outflow, and results in the stasis of blood in the tissues that are normally drained by the affected veins. The resultant lack of tissue perfusion causes hypoxia, acidosis, and arterial thrombi formation, which can potentially progress to tissue necrosis and wet gangrene. In the past several decades, the use of leeches (Hirudo medicinalis) has been rediscovered as an effective method of relieving acute venous congestion. This updated review of leech therapy focuses on the use of medicinal leeches in a variety of clinical conditions characterized by acute venous congestion, and points out the experimental use of leeches in other pathological entities. A discussion of the recent scientific findings that explain the possible mechanisms of action of leech therapy is also provided.

Midterm follow-up of midface distraction for syndromic craniosynostosis: a clinical and cephalometric study.

Background: The authors studied the effect of midface distraction on maxillary skeletal position and clinical appearance in patients with Crouzon, Pfeiffer, and Apert syndromes, and examined the stability of these changes at 1 year after distraction. Methods: Fifteen consecutive patients (six male and nine female; average age, 5.9 years) underwent Le Fort III osteotomy with midface advancement using a rigid external distraction device. Six patients had Crouzon, five had Pfeiffer, and four had Apert syndrome. Midface advancement was initiated at the level of the occlusal splint and at the zygomatic/maxillary anchor screws. The device was activated 11 mm on average, at a rate of 1 mm per day. Twenty anatomical landmarks were identified and digitized at three time intervals, and displacement of each landmark was compared with its pretreatment position. Results: By the time of device removal, point A had advanced sagittally along the x axis 15.85 mm and moved downward 1.06 mm along the y axis; the orbitale was moved sagittally along the x axis 12.72 mm and downward 1.99 mm along the y axis. Maximum mean advancement (17.16 mm) was observed at the upper incisal edge. Maxillary and mandibular skeletal discrepancy was significantly decreased, with the ANB angle changing from −5.87 to +13.17 degrees. At 1 year after distraction, point A had advanced an additional 0.81 mm, and the orbitale and upper incisal edge had moved posteriorly 0.07 mm and 1.34 mm, respectively. Conclusion: Significant midface advancement can be achieved and maintained with rigid external distraction of the Le Fort III osteotomy segment (up to 24 mm), with excellent stability of the advanced midfacial skeleton.

Antibody to transforming growth factor beta reduces collagen production in injured peripheral nerve

&NA; Epineurial scarring in peripheral nerve after injury inhibits normal axonal regeneration primarily due to fibroblast deposition of type I collagen. The transforming growth factor beta (TGF‐&bgr;) family is an important class of signaling molecules that has been shown to stimulate fibroblasts to produce collagen. The aim of this study was to design a prototypic therapeutic system in which the neutralization of TGF‐&bgr; in crushed rat sciatic nerve would decrease collagen formation. A total of 45 experimental Lewis rats were used. Group 1 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate buffer solution. Group 2 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate‐buffered saline and goat, anti‐rat, panspecific TGF‐&bgr; antibody. Group 3 control animals (five rats) underwent only exposure of sciatic nerve with injection of antibody. All animals were killed at 14 days and sciatic nerve specimens were harvested at that time. Slides of experimental tissue were processed using a 35S‐labeled oligomer for procollagen alpha‐1 mRNA, then dipped in photographic emulsion and examined by darkfield autoradiography. Morphometric analysis of pixel counts was then performed. A significant reduction in total pixel count per high‐power field and in total number of fibroblasts per high‐power field was found in crushed rat sciatic nerve treated with anti‐TGF‐&bgr; antibody when compared with those treated only with phosphate‐buffered saline. These findings are consistent with successful reduction in procollagen induction after a crush injury by topical administration of blocking antibody against transforming growth factor beta. The concept of growth factor blockade for therapeutic collagen reduction is attractive in the context of nerve injury, and the current article provides a model for future clinical application. (Plast. Reconstr. Surg. 102: 1100, 1998.)

The Intradermal Anatomy of the Inframammary Fold

&NA; The anatomy of the inframammary fold has been a subject of controversy. This report describes the anatomic location and the histologic structure of the inframammary fold on the basis of caderveric dissections and microscopic examination. Ten breast cadaver dissections were performed on female cadavers (ages 35 to 72). Twenty specimens after en bloc resections of the inframammary fold and subcutaneous tissue, including the pectoralis muscle, were harvested. Specimens were examined for gross collagen structure by using India ink to highlight the collagenous aspects of the subcutaneous soft‐tissue networks. The inframammary fold skin and dermis from the contralateral breast and control samples of skin and dermis from the upper chest and the abdomen were collected for microscopic studies. These samples were stained with Sirius red and examined microscopically by polarized light. On histologic examination, regular arrays of collagen were found running parallel with the inframammary fold, and the control sections showed random patterns of collagen deposition. On gross examination, a condensation of the superficial fascial system was observed. This formed a zone of adherence between the skin and the underlying pectoralis fascia. The conclusion of this study is that the inframammary fold is an intrinsic dermal structure consisting of regular arrays of collagen held in place by a zone of adherence that is a specialized area of the superficial fascial system. The clinical significance of this study is that the intradermal structure of the inframammary fold should be preserved in any breast procedure for natural aesthetic results. (Plast. Reconstr. Surg. 102: 1030, 1998.)

Cheek and eyelid reconstruction: the resurrection of the angle rotation flap.

Background: Reconstruction of larger cheek and eyelid defects may pose a dilemma for surgeons, since flaps used in reconstruction may be difficult to design, be unreliable, require extensive dissection, and result in neck scarring. Consequently, the authors wish to simplify and expand an overlooked flap, the angle rotation flap, which moves tissue in both a medial and upward direction. Methods: Twenty patients with cheek and eyelid defects were treated by the angle rotation flap. In this flap design, the angle designed below the ear was closed primarily and the neck tissue previously there was rotated upward and forward to lie in front of the ear. The portion of the flap that was in front of the ear was transposed to the lower lid/cheek area. This flap was modified in several patients by elevation in the deep plane and first-stage tissue expansion. Results: In all cases, good coverage was provided for medial cheek and lower eyelid defects with minimal scarring on the neck. There were no flap losses of any kind. There were no major complications, and all minor incidences were treated by minimal procedures without long-term sequelae. Conclusion: The modified angle rotation flap is a useful tool for cheek and eyelid defects.

Chin surgery III: Revelations

This article is a logical extension of previous articles written on the topic of aesthetic chin surgery. In it, the authors expand on previously published surgical techniques and provide specific updates to increase success in some unusual situations. They review the indications for and uses of reduced-height implants, discuss the validity of centralized chin incisions in both reconstruction and revisions, show the diversity of mentalis muscle anatomy and chin pad variations, reveal the importance of the lip-to-labiomental crease inclination in cases of macrogenia, note a key update on reefing the mentalis muscle to a higher position for permanent sulcus position, discuss the issues of lower lip position and lower incisor show, and expound on the horizontal smile/chin ptosis phenomenon.

Double venous system drainage in deep inferior epigastric perforator flap breast reconstruction: a single-surgeon experience.

Background: Breast reconstruction with the deep inferior epigastric perforator (DIEP) flap has many advantages. The main drawback is the technical difficulty and risk of failure. Many flap failures are the result of venous insufficiency. The author explored the routine use of double venous system anastomosis in DIEP flap breast reconstruction. Methods: In all consecutive DIEP flaps performed by the author from June 1, 2008, to July 1, 2012, in which it was technically feasible, a superficial vein was dissected and anastomosed to either an internal mammary perforating vein or a second vena comitans. Patient charts were reviewed for flap failure or return to the operating room for exploration of suspected vascular insufficiency. A standard chi-square test and Yates corrected chi-square test were used for analysis. Results: Three hundred fifty-two DIEP flaps were performed on 192 patients in the study period. In 311 of 352 flaps (88.4 percent), double venous system anastomosis was possible. There were no flap failures in either group. In the double venous system group, there was one (0.3 percent) return to the operating room for venous congestion. In the single venous system group, there were two (4.9 percent). Chi-square analysis showed statistically significant reduction in operative explorations in the double venous system group (value of 8.9; p = 0.0029). A Yates correction, applied because of the low number of reoperations in both groups, also showed a statistically significant reduction (value of 4.3; p = 0.038). Conclusion: Double venous system anastomosis statistically reduced operative take-backs in this study.