Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-␤ in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1؊/؊ C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-␤ activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-␤ activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-␣ induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis. (Am J Pathol 2005, 167:365-379) Idiopathic pulmonary fibrosis (IPF), with its histopathological signature of usual interstitial pneumonia (UIP), is a paradigmatic, but as yet primarily enigmatic example of uncontrolled fibroproliferation. IPF is remarkable for its insidious onset, dramatic histopathological and pathophysiological derangements, and relentless progression to death regardless of treatment. The etiology of IPF, and the factors that direct its dismal outcome, remain the subject of intense investigation.1 Fibroblasts are the cellular sine qua non of fibrosis in most tissues, and the histopathology of IPF underscores this observation. The histopathological feature most clearly correlated with outcome is the presence in lung of fibroblastic foci of young connective tissue, the presence of which portends death within months.2 Fibroblastic foci seem to represent the fibroproliferative leading edge of the heterogeneous areas of scarring in IPF.3-5 The myofibroblasts within these foci are clearly dysregulated in their proliferative and matrix-productive function, yet the origin of these cells, and the factors that lead to their accumulation and persistence, are unknown.Fibroblasts in most tissues are heterogeneous with respect to size, secretory profile, and surface markers. Fibroblasts within a fibrogenic milieu clearly differ from those in normal tissues. In particular, fibroblasts isolated from lungs with active fibrotic disease have increased proliferative capacity, are capable of anchorage-independent growth, and are morphologically distinct. 6 -8 Furthermore, differences among subsets of normal fibroblasts have been identified on the basis of surface markers, cytoskeleta...

Thy-1 is a glycosylphosphatidyl-inositol-linked cell surface glycoprotein whose exact biological role remains unclear. Differential expression of Thy-1 affects fibroblast proliferation and fibrogenic signaling. In idiopathic pulmonary fibrosis, the proliferating myofibroblasts within the fibroblastic foci are Thy-1(-), whereas normal lung fibroblasts are predominantly Thy-1(+). In this study, we used rat lung fibroblasts sorted for Thy-1 expression to examine myofibroblastic differentiation in response to fibrogenic stimuli. We examined the effects of transforming growth factor-beta, endothelin-1, and connective tissue growth factor on the expression of myofibroblast proteins and myogenic regulatory factors by real-time RT-PCR and immunoblotting. Thy-1(-) cells have significantly higher myofibroblast and myogenic regulatory factor gene and protein expression compared with Thy-1(+) cells, confirmed by immunofluorescence. We also used floating collagen matrix contraction assays to assess the functional differentiation of the fibroblasts. At baseline and after stimulation with transforming growth factor-beta and endothelin-1, Thy-1(-) cells caused significantly greater collagen contraction than did Thy-1(+) cells, supporting the hypothesis that Thy-1(-) cells are more fully differentiated myofibroblasts. Because apoptosis has been implicated in the regression of myofibroblasts, we examined the percentage of apoptotic cells in the contracted collagen matrices at baseline and after stimulation with fibrogenic agents. A significantly greater proportion of Thy-1(+) cells underwent apoptosis in all conditions compared with Thy-1(-) fibroblasts. Transfection of Thy-1 into Thy-1(-) cells inhibits collagen matrix contraction and reduces cell survival. Our data indicate that Thy-1 regulates myogenic gene expression, myofibroblastic differentiation, and survival in lung fibroblasts.

Breast augmentation is consistently one of the most commonly performed aesthetic operations every year. Unfortunately, revision rates following primary augmentation remain as high as 36%. There are several causes for revision breast augmentation; however, the most common and challenging of these include capsular contracture, implant malposition, and ptosis of the aging breast following augmentation. Successful management of these problems requires knowledge on how to best treat the implant and capsule with the corresponding soft tissue simultaneously. While surgical management is important, understanding the pathological causes of these entities during the primary operation can reduce the need for revision. This article utilizes the most up-to-date literature to review the appropriate clinical evaluation and surgical management of these complex cases.

Background In immediate breast reconstruction, the plastic surgeon must strive to create an aesthetically pleasing result while minimizing complications. The latissimus dorsi (LD) myocutaneous flap has long been used a workhorse flap in breast reconstruction. Often times, it is used a salvage flap after other methods of breast reconstruction have failed. In this study, we review the use of this flap in conjunction with prosthetic devices, regardless of the need for adjuvant radiation, to determine the safety and efficacy of this approach as a primary method of reconstruction. Methods A single surgeon practice with a standardized reconstructive algorithm was reviewed. This compromises a 2-stage approach involving the use of LD myocutaneous flaps and tissue expanders for immediate reconstruction after mastectomy, followed by exchange for implants at a secondary surgery. A retrospective chart review was performed on 201 patients (376 breast reconstructions) who met inclusion criteria. Patient demographics and outcomes were compared based on radiation status. The primary outcome, reconstructive success, was defined as no need for further autologous reconstruction beyond the 2-stage approach utilized. Results Statistical analysis was performed on both patient demographics, complications, and reconstructive outcomes. Demographics were equivalent between the 2 groups. When analyzing complications and outcomes, there was no difference between nonradiated patients and radiated patients except when looking at reconstructive loss, which was 3.6% in the nonradiated group and 16.6% in the radiated group (P = 0.03). However, one third of the patients in the radiated group who had reconstructive losses were due to reasons not related to radiation therapy. Taking this into account, overall reconstructive success showed no statistical significance between the 2 groups. Conclusions The findings from this study show that immediate reconstruction with LD myocutaneous flaps in conjunction with prosthetic devices is a reliable and safe option, even in the setting of adjuvant radiation therapy, as the autologous tissue mitigates many sequelae of radiation therapy. Not only does this type of reconstruction provide an aesthetically pleasing result in 2 stages, but also has a favorable complication profile and success rate.

Breast cancer affects 1 in 8 women. As the treatment of breast cancer evolves, breast reconstruction does as well. Implant-based reconstructions are increasing, leading to increased use of acellular dermal matrix (ADM) for better implant positioning. Acellular dermal matrices are derived from cadaveric skin and are processed to be immunologically inert. However, ADM can be costly and can have complications such as seroma and infection. This has led to the development of dermal autografts. These were first used in postmastectomy breast reconstruction in women with redundant breast skin that was deepithelialized and used for lower pole coverage of tissue expanders and implants. This evolved into harvesting dermal autografts from the abdomen. Later studies evaluated the use of meshed dermal autografts. Histological analysis of ADM versus dermal autografts shows that there are increased vessels within dermal autografts compared with ADM. This potentially contributes to the decreased complication rate seen with autografts. In addition, one study showed equivalent results in aesthetic outcomes and capsular contracture between ADM and dermal autograft. Analysis of cost has shown that ADM is significantly more costly than harvesting a dermal autograft. Physician reimbursement is also higher for dermal autografts. This review article seeks to summarize key studies that highlight the feasibility of using dermal autografts in breast reconstruction.

Background The profunda artery perforator (PAP) flap has been demonstrated to be an effective method of autologous breast reconstruction, particularly when the abdominal donor site is contraindicated. However, there are no current reports regarding the use of a sensate PAP flap in this type of reconstruction. The objective of this study is to describe the feasibility and anatomic location of the sensory nerves supplying the PAP flap in relation to surface landmarks for use in autologous breast reconstruction. Methods In this anatomic study, 10 cadaver lower limbs were microsurgically dissected. We investigated the posterior femoral cutaneous nerve (PFCN), which supplies sensation to the skin of the posterior thigh and distribution of the PAP flap. The midline of the posterior thigh and gluteal crease were used for surface landmarks. The diameter and length of the nerve branches were documented. Results There were between 2 and 5 PFCN branches, with an average of 3 branches, that were found within the distribution of the PAP flap. Measurements were taken from the gluteal crease and midline to the nerve branches. The average distance caudal to the gluteal crease was 2.4 cm (0 to 7 cm). The average distance medial to the midline was 4.3 cm (0.2 to 8.1 cm). The average diameter of the nerve branches was 1.8 mm (1 to 2.5 mm). The average length of nerve branches from the flap to the fascia was 2.0 cm (1.5 to 2.4 cm). The maximum length of the nerve branches from the flap to the main trunk of the PFCN was 7.8 cm when tracing the nerve branches intramuscularly. Conclusions The findings from this study provide an anatomic basis for the sensate PAP flap that would potentially provide an additional dimension to the use of this perforator flap in autologous breast reconstruction. These preliminary results are promising, and further physiological studies are warranted to validate the use of this sensate flap.

Summary:Mucormycosis is a rare fungal infection in immunocompetent patients. It is not commonly seen in trauma patients who sustain multisystem injuries and are often exposed to numerous infectious sources. A multidisciplinary approach between medical and surgical specialties is crucial to ensuring timely diagnosis and treatment as morbidity and mortality can be high once acquired. In addition to antifungal therapy, radical debridement and reconstruction by plastic surgery is often necessary. Review of the literature shows that there is no definitive reconstructive technique for mucormycosis of the forehead and sinuses because the amount of tissue destruction may be varied in location and depth, therefore requiring varying extents of debridement. However, other reconstructive techniques commonly used for oncologic and trauma reconstructions can be used to achieve functionality and a satisfactory cosmetic result. Few facial reconstructions after infection with mucormycosis have been documented in the literature.

Summary:Congenital melanocytic nevus of the hand in the pediatric population is an uncommon diagnosis. These lesions have malignant potential and can cause psychosocial effects from cosmetic deformity. Early surgical intervention is recommended in these cases. The literature suggests that full-thickness skin grafting is to be performed in the hand to maintain functionality and avoid contracture and scarring. This creates a large donor-site defect and increased risk of graft loss due to slow revascularization from graft thickness. In addition, for large defects, the full-thickness skin graft donor site would require a split-thickness graft. However, split-thickness skin grafting is avoided in the hand due to increased scarring and contracture and decreased range of motion despite decreased donor-site morbidity and better revascularization. We describe a novel reconstructive technique that uses a dermal regenerative template (Integra) with split-thickness grafting. Having performed in 2 pediatric patients, we demonstrate that aesthetic and functional outcomes are equivalent to full-thickness grafting while creating a superficial donor site and allowing for improved revascularization from decreased graft thickness.