Growing skin: tissue expansion in pediatric forehead reconstruction

Tissue expansion is a common surgical procedure to grow extra skin through controlled mechanical over-stretch. It creates skin that matches the color, texture, and thickness of the surrounding tissue, while minimizing scars and risk of rejection. Despite intense research in tissue expansion and skin growth, there is a clear knowledge gap between heuristic observation and mechanistic understanding of the key phenomena that drive the growth process. Here, we show that a continuum mechanics approach, embedded in a custom-designed finite element model, informed by medical imaging, provides valuable insight into the biomechanics of skin growth. In particular, we model skin growth using the concept of an incompatible growth configuration. We characterize its evolution in time using a second-order growth tensor parameterized in terms of a scalar-valued internal variable, the in-plane area growth. When stretched beyond the physiological level, new skin is created, and the in-plane area growth increases. For the first time, we simulate tissue expansion on a patient-specific geometric model, and predict stress, strain, and area gain at three expanded locations in a pediatric skull: in the scalp, in the forehead, and in the cheek. Our results may help the surgeon to prevent tissue over-stretch and make informed decisions about expander geometry, size, placement, and inflation. We anticipate our study to open new avenues in reconstructive surgery and enhance treatment for patients with birth defects, burn injuries, or breast tumor removal.     

Complications of controlled tissue expansion in the pediatric burn patient

All patients at the Burn Institute reconstructed with tissue expanders between June of 1984 and June of 1987 were included in this review. There were 122 expanders used in 77 patients. Complications were defined as "absolute" (23 of 122 expanders, 20 percent) if they resulted in loss of expanders or additional surgery or none of preoperative plan was satisfied or "relative" (14 of 122 expanders, 11 percent) if they included spotty alopecia or alopecia greater than 50 percent or the operative plan only partially satisfied, reflecting poor judgment. The most common absolute complication was prosthetic exposure secondary to wound dehiscence occurring in the scalp area. Complications relative to specific anatomic areas were neck and face, 2 of 20 (10 percent); lower extremity, 1 of 4 (25 percent); trunk, 0 of 6 (0 percent); and scalp, 20 of 92 (22 percent). We feel that this high complication rate in the use of tissue expanders may be unique to the pediatric burn patient. Knowledge of indications for use and potential complications is essential to add this entity to the armamentarium of the burn reconstructive surgeon.     

Adjunctive treatment of congenital pigmented nevi with phenol chemical peel

The purpose of this study was a retrospective evaluation of the treatment of congenital pigmented nevi using the phenol chemical peel technique. Patients were treated with standard Baker formula in the operating room under general anesthesia or intravenous sedation with continuous electrocardiogram monitoring. A total of 20 patients were reviewed (13 girls and 7 boys, mean age 3.8 years). Eight patients had nevi located on the face, five patients had trunk lesions, and three patients had lesions on the thighs. Two patients had nevi located on both the face and the trunk, and two patients had involvement of the face, trunk, and thigh. Three of the above patients had the classic "bathing trunk" distribution of the nevi. A test area was peeled in four patients, and in five patients preoperative biopsies were performed to rule out malignancy before initiation of therapy. An average of 2.6 treatments were performed per patient. Two patients had adjunctive dermabrasion to increase the depth of peel and to contour surface irregularities. The length of follow-up ranged from 6 to 84 months with a mean of 28 months. Healing of the wounds occurred within 2 to 3 weeks postoperatively. Seventy-five percent of patients had satisfactory cosmetic improvement in the appearance of the lesions following treatment. Four patients had recurrence of the pigmentation after an initial lightening response, three of whom had their nevi subsequently excised. There was no incidence of hypertrophic scarring or cardiac and/or renal complications. There was one death from complications of leptomeningeal melanocytosis. Chemical peeling of congenital pigmented nevi is an acceptable alternative method of therapy for those lesions that are too large for excision and primary closure or for lesions in which excision would result in unacceptable scars in areas such as the face.     

An ex vivo study of congenital pigmented nevi in epidermal reconstructs.

In order to study morphologic and functional characteristics of pigment cells in congenital pigmented nevi, autologous or heterologous reconstructs have been made using normal keratinocytes and nevus cells from the dermal-epidermal junction or from the dermis. All these cells, keratinocytes and nevus cells, were used as cell suspensions immediately after dissociation from the tissues or after subsequent brief cultivation in a serum-free medium. Reconstructed epidermis were cultured for 15 days at the air-liquid interface with or without ultraviolet (UV) B exposure. The reconstructs were examined macroscopically (formation of hyperpigmented macules), histologically (pigment cell nesting) and ultrastructurally (pigment structure and transfer). Typical nesting of nevus cells was observed in the dermal-epidermal junction or in the superficial dermis associated with macroscopically detectable small pigmented macules. UVB exposure induced an upward migration of nevus cells in the suprabasal layers of the epidermis. This tissue model can be considered as an excellent system for the ex vivo reproduction of pigmented nevi and as an assay of the sensitivity of nevus cells towards UVB irradiation.     

Risk of melanoma arising in large congenital melanocytic nevi: a systematic review

Large congenital melanocytic nevi are cutaneous lesions regarded by many as premalignant; estimates of malignancy incidence range from 0 to 42 percent. Given the often complex and extensive nature of large congenital melanocytic nevi resection and reconstruction, the risk of malignant transformation is a crucial factor that surgeons and families must weigh when deciding whether or not to excise the lesion. The authors conducted a systematic analysis of data from the existing literature to critically evaluate the published studies and to establish a crude incidence rate for the risk of malignant melanoma transformation in large congenital melanocytic nevi. After a comprehensive literature search, they analyzed data from eight studies (containing a total of 432 large congenital melanocytic nevi patients) of sufficient scientific quality. Twelve patients (2.8 percent) in this sample developed cutaneous malignant melanoma during the reported follow-up periods. Using a subset of this data and comparing the incidence rates to those of the Surveillance, Epidemiology, and End Results population-based database using a standardized morbidity ratio, the authors found that the large congenital melanocytic nevi patients had an increased risk of melanoma (standardized morbidity ratio, 2599; 95 percent confidence interval, 844 to 6064) compared with the general population. Regarding treatment before developing melanoma in the 12 patients, 50 percent were observed before diagnosis, 17 percent had partial excision, 8.3 percent had dermabrasion, 8.3 percent had a chemical peel, and 17 percent did not have any treatment information. These combined data are clinically useful when consulting with the parents of children with large congenital melanocytic nevi and in the management of older patients with existing lesions. This study shows that there is a significantly increased risk of melanoma in large congenital melanocytic nevi patients. The data also reveal the need for a standardized definition of large congenital melanocytic nevi and a long-term, prospective outcomes study to determine the true lifetime risk of melanoma in patients with and without surgical excision.     

The role of tissue expansion in the treatment of atypical facial clefting

Tissue expansion can be a valuable tool in the reconstruction of soft-tissue defects in craniofacial clefts. To our knowledge, there have been no reports in the literature of the use of tissue expanders to help solve this problem. We report the case of a child with an atypical Tessier no. 3 craniofacial cleft who had a forehead tissue expander placed, inflated, and thus used to provide sufficient local facial skin for repair of the soft-tissue defect.     

Ventricular tachycardia in the setting of a large cardiac fibroma in a pediatric patient

Ventricular tachycardia and cardiac tumors are both extremely rare diagnoses in pediatric patients. We report a pediatric case of cardiac fibroma that was noted during the work up of ventricular tachycardia in a young patient concomitantly diagnosed with severe acute respiratory syndrome coronavirus 2.     

Nucleolar organizer regions in pigmented skin lesions. Value in the differential diagnosis of Spitz nevi.

Forty-one cases of typical melanocytic skin lesions (15 intradermal nevi, 14 Spitz nevi and 12 malignant melanomas) were used to investigate the value of staining of nucleolar organizer regions (NORs) in the differential diagnosis of such pigmented lesions. Histologic sections were stained by the silver colloid (Ag) method, with and without the prior use of a melanin blocking agent. There were statistically significant differences in the mean numbers of AgNORs per nucleus between the groups of lesions studied (1.658 for intradermal nevi, 3.0042 for Spitz nevi and 6.669 for malignant melanomas). Sections treated with potassium permanganate (melanin blocking agent) prior to staining showed an obvious increase in the AgNOR scores in all groups; this increase was highest for Spitz nevi. Although AgNOR staining allows a distinction to be made between intradermal nevi and malignant melanomas, the striking overlap between the counts for Spitz nevi and malignant melanomas precludes the use of this technique as the sole method for establishing the diagnosis of malignancy. Other clinical and morphologic data are especially required to make the diagnosis of Spitz nevi.     

Current advances in the translation of vascular tissue engineering to the treatment of pediatric congenital heart disease

Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism behind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.     

Dermal nevus cells from congenital nevi cannot penetrate the dermis in skin reconstructs

Congenital nevi are composed of pigment cells bearing common features with melanocytes but showing altered differentiation which leads to nesting and dermal involvement. Using a dead de-epidermized dermis seeded with a combination of keratinocytes and various sources of pigment cells (normal melanocytes, dermal nevus cells from congenital nevi, Bowes melanoma cells), we have studied the formation of nests and the dermal migration of pigment cells together with their secretion profiles of matrix metalloproteinases (MMP). Dermal fibroblasts were also used as control cells in epidermal reconstructs. Besides their morphologic features, the absence of pigment donation to keratinocytes was the major characteristic of dermal nevus cells. A positive correlation was established between the increasing percentage of seeded nevus cells and the patchy pigmentation of reconstructs, as well as the clustering of cells in junctional nests. However, the presence of nevus cells in the dermis of reconstructs was never detected, whereas melanoma cells and dermal fibroblasts could invade the dermis during the time span of the experiments. MMP9 was never expressed in congenital dermal nevus cells but pro-MMP2 was constitutively expressed by all strains of congenital nevus cells and dermal fibroblasts. Melanocytes produced comparable amounts of both pro-MMP2 and pro-MMP9, and Bowes melanoma cells secreted a marginal level of pro-MMP2. In view of their three-dimensional behaviour and secretion of MMPs, we propose that dermal congenital nevus cells correspond to an intermediate status of differentiation between normal melanocytes and melanoma cells. Activation of MMPs by a cofactor or the activation of another signalling pathway seems necessary to induce the dermal passage of nevus cells.