Head and neck malignant melanoma: local recurrence rate following wide local excision and immediate reconstruction.

Excision of head and neck melanoma is often limited by critical structures, which can lead to incomplete excision with positive pathologic margin and increased local recurrence rate. Complete excision with recommended margins and immediate reconstruction is possible when surgical oncologists and plastic surgeons work collaboratively. Our purpose was to evaluate local recurrence rate after excision and immediate reconstruction. We reviewed 98 consecutive patients treated for primary head and neck cutaneous melanoma at a single institution between 1999 and 2004. We assessed local recurrence rate. A total of 72 patients (73%) were followed for an average of 5.2 ± 1.7 years while 26 patients were excluded due to less than 1 year of follow-up. Adjacent tissue transfer was the most common reconstruction (87%). Local recurrence was reported in 2.8% and distant metastasis in 12.5% of patients. Immediate reconstruction after excision of head and neck melanoma can be safely performed with low local recurrence rate.

Mesenchymal stem cells induce dermal fibroblast responses to injury.

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

Substance P enhances wound closure in nitric oxide synthase knockout mice.

INTRODUCTION: The neuropeptide, substance P (SP), up-regulates nitric oxide production (NO). The purpose of this study was to determine whether SP enhances response to cutaneous injury in nitric oxide synthase knockout (NOS null) mice. METHODS: We studied mice with targeted deletions of the 3 NOS genes, neuronal NOS, inducible NOS, or endothelial NOS. Full thickness dorsal wounds were treated daily (d 0-6) with topical SP or normal saline (NaCl). Wounds were analyzed by flow cytometry for macrophage, leukocyte, endothelial, and dendritic cells. Healing time and wound epithelialization were compared using analysis of variance. RESULTS: Wound closure in the 3 NOS null mice was slower than the control mice (P < 0.05). SP treatment enhanced wound closure in NOS null mice (P < 0.02). NOS null wounds exhibited reduced inflammation. SP increased macrophage, leukocyte, and dendritic cell densities at d 3 and d 7 (P < 0.05) in all NOS null mice. SP increased endothelial cell number in neuronal NOS and inducible NOS null mice, but not in endothelial NOS null mice (P > 0.05). CONCLUSIONS: SP ameliorated the impaired wound healing response observed in NOS null mice by enhancing wound closure kinetics and epithelialization. SP increased inflammatory cell density in the wounds supporting the essential role of inflammatory cells, especially macrophages, in wound repair.

Patient body mass index and perforator quality in abdomen-based free-tissue transfer for breast reconstruction.

Body mass index (BMI) must be considered when selecting patients suitable for abdomen-based microsurgical breast reconstruction. It is unknown whether BMI or age affects quality or quantity of abdominal wall perforating blood vessels. The purpose of this study was to identify differences in abdominal wall perforating blood vessels among patients with different BMI and age. A retrospective review was conducted of 66 patients undergoing abdomen-based microsurgical breast reconstruction tissue transfer from 2000 to 2006. Median age was 48.6 years (+/- 8.2). Patients were divided into BMI < 25 (28 patients), BMI 25 to 30 (26 patients), or BMI > 30 (12 patients). Perforator size and location was determined by ultrasound data. There was a greater number of perforators in horizontal zone II compared with the remaining zones (P < 0.05, Bonferroni corrected). There were no differences between age or BMI and the number of perforators or average perforator size per patient. A significant positive linear association was found between the average perforator diameter and total number of abdominal wall perforators. We concluded there is no anatomical difference in perforator quality among patients with varying BMIs

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds.

The neuropeptide substance P (SP) is a known inflammatory mediator released from cutaneous peripheral nerve terminals. SP effects on cellular composition in the cutaneous response to injury remain unclear. Based on our previous observations about SP effects on wound repair, we hypothesized that topical SP increases inflammatory cell density infiltration early after injury. A full-thickness 1.5 x 1.5 cm(2) wound was created on the dorsum of 8-9-week-old C57BL/6J-m+Lepr(db) mice (db/db). Wounds were treated daily with 300 muL of either normal saline (0.9% NaCl) or 10(-9) M SP for 7 days. Three wounds from each group were harvested at 2, 3, 7, 14, and 28 days. Samples underwent enzymatic digestion and were incubated with fluorescent-labeled antibodies. Using flow cytometry, cellular content and density for each sample was derived. Masson Trichrome stained histology specimens were prepared to confirm results. Cell density in the SP-treated wounds (11.3 x 10(7) cells/g tissue, standard deviation [SD]+/-1.5 x 10(7)) was greater than in NaCl-treated wounds (7 x 10(7) cells/g tissue, SD+/-2.3 x 10(7), p<0.05) at day 7 postwounding. SP significantly increased the density of leukocytes (2.1 x 10(7), SD +/-3.6 x 10(6) vs. 1.8 x 10(7), SD+/-4.9 x 10(5), p<0.02) 3 days after wounding and the density of macrophages (2.9 x 10(7), SD+/-7.5 x 10(6) vs. 1.3 x 10(7), SD+/-1.4 x 10(6), p<0.05) 7 days after wounding. There were no significant differences in endothelial cell, leukocyte, or macrophage density at later time points. Topical SP treatment increases early inflammatory density in the healing wounds of db/db mice. These data support a role for nerve-mediated inflammation in cutaneous wound repair.

True incidence of all complications following immediate and delayed breast reconstruction.

BACKGROUND: Improved self-image and psychological well-being after breast reconstruction are well documented. To determine methods that optimized results with minimal morbidity, the authors examined their results and complications based on reconstruction method and timing. METHODS: The authors reviewed all breast reconstructions after mastectomy for breast cancer performed under the supervision of a single surgeon over a 6-year period at a tertiary referral center. Reconstruction method and timing, patient characteristics, and complication rates were reviewed. RESULTS: Reconstruction was performed on 240 consecutive women (94 bilateral and 146 unilateral; 334 total reconstructions). Reconstruction timing was evenly split between immediate (n = 167) and delayed (n = 167). Autologous tissue (n = 192) was more common than tissue expander/implant reconstruction (n = 142), and the free deep inferior epigastric perforator was the most common free flap (n = 124). The authors found no difference in the complication incidence with autologous reconstruction, whether performed immediately or delayed. However, there was a significantly higher complication rate following immediate placement of a tissue expander when compared with delayed reconstruction (p = 0.008). Capsular contracture was a significantly more common late complication following immediate (40.4 percent) versus delayed (17.0 percent) reconstruction (p < 0.001; odds ratio, 5.2; 95 percent confidence interval, 2.3 to 11.6). CONCLUSIONS: Autologous reconstruction can be performed immediately or delayed, with optimal aesthetic outcome and low flap loss risk. However, the overall complication and capsular contracture incidence following immediate tissue expander/implant reconstruction was much higher than when performed delayed. Thus, tissue expander placement at the time of mastectomy may not necessarily save the patient an extra operation and may compromise the final aesthetic outcome.

Resection of panniculus morbidus: a salvage procedure with a steep learning curve.

BACKGROUND: A subset of obese people develop a pannus hanging to the floor. This panniculus morbidus prevents weight loss, as the patient cannot exercise. It prevents hygiene, leading to a profound odor and ultimately results in intertrigo, cellulitis, and/or abdominal ulceration. The only two options are to live/die with it or resect it. Some of these people are otherwise ready for a weight loss program. For this group, resection of the panniculus morbidus may be indicated. The authors reviewed the literature and found the condition has not been addressed in this Journal since 1994 and was not considered in the recent supplement on body contouring. In 1998, the authors began resecting panniculus morbidus for this small group. The authors found the learning curve to be profoundly steep, with many wound complications, a finding that is quite in conflict with the literature on the subject, and decided to present their experience. METHODS: The authors conducted a retrospective chart review of 23 patients and collected data on demographics, ambulation, hygiene, technique, complications, and outcome. RESULTS: The technique of closure evolved as the authors struggled with complications. The current method of closure is three suture layers over four suction drains with a small wound vacuum-assisted closure device at each end of the incision. All patients ultimately healed and found it easier to ambulate and perform hygiene. CONCLUSION: Resection of panniculus morbidus is a beneficial salvage procedure for some morbidly obese people, but the learning curve is steep and the current literature is misleading.

Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring.

Hypertrophic scarring after burns is an unsolved problem and remains as devastating today as it was in the 40s and it may be that the main reason for this is the lack of an accepted, useful animal model. The female, red Duroc pig was described as a model of hypertrophic scarring nearly 30 years ago but then vanished from the literature. This seemed strange since the authors reported that 12 of 12 pigs developed thick scar. In the mid 90s we explored the model and found that, indeed, the red Duroc pig does make thick scar. Other authors have established that the Yorkshire pig does not heal in this fashion so there is the possibility of a same species control. We have continued to explore the Duroc/Yorkshire model and herein describe our experiences. Is it a perfect model of hypertrophic scarring? No. Is it a useful model of hypertrophic scarring? Time will tell. We have now obtained gene expression data from the Duroc/Yorkshire model and analysis is underway.

Breast implant capsules are partially composed of bone marrow-derived cells.

Capsular contracture is the most common complication following breast augmentation or reconstruction with implants. We recently demonstrated that bone marrow-derived cells provide fibroblasts to murine skin during wound healing. To determine if bone marrow-derived cells were the cellular source of periprosthetic capsules, we created chimeric C57BL mice containing bone marrow cells from isogeneic enhanced green fluorescent protein (EGFP) mice and implanted with a textured silicone shell implant. We found that none of the mice developed infection or capsular contracture, but day 30 capsules were composed of 26.4 +/- 6.1% EGFP cells, and day 60 capsules had 21.8 +/- 10.3% EGFP cells. Immunohistochemistry revealed a small population of EGFP cells in the capsules that were myofibroblasts. Thus, breast implant capsules are partially composed of bone marrow-derived cells and, given the potential of these cells to become myofibroblasts, may explain the cellular source of capsular contracture when it develops.

Utility of the free deep inferior epigastric perforator flap in chest wall reconstruction.

Breast cancer chest wall recurrence is often treated with chemotherapy, radical surgery, and radiation. Extensive chest wall resection requires soft-tissue reconstruction with tissue that provides chest wall stability and durability for additional radiation. Local and regional muscle and musculocutaneous flaps are often used for reconstruction. Free flaps, such as the transverse rectus abdominis musculocutaneous flap, are used for large defects, although donor site morbidity can result. The free deep inferior epigastric perforator (DIEP) flap provides coverage for large defects and may have less donor site morbidity. We describe the use of the free DIEP flap to reconstruct large chest wall defects (mean, 501 cm2 defects) after the resection of recurrent breast cancer in two patients. One patient had 2% flap loss. No donor site morbidity occurred. The free DIEP flap is a durable and reliable flap that provided immediate and complete coverage of these large chest wall defects with no donor site morbidity and did not delay the administration of adjuvant therapy.

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis "knows" how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar.

Does the use of a flap during abdominoperineal resection decrease pelvic wound morbidity?

We hypothesized that the use of muscle flaps, known as tissue transfer (TT), at the time of abdominoperineal resection (APR) reduces perineal wound complications. A restrospective review of patients undergoing an APR at the University of Washington (1984-2003) was conducted. Perineal wound complications and eventual wound healing were compared in patients with and without TT. Ninety-two patients (mean age, 56.6 years) underwent APR; 23.9 per cent (n = 22) had concurrent TT. Patients undergoing TT were more likely to have cancer (91% vs. 77%, P = 0.05) and radiation therapy (86% vs. 52%, P < 0.01). Operative times were nearly 2 hours longer in patients having TT (7.4 hours +/- 2.5 hours vs. 5.6 hours +/- 1.8 hours, P = 0.03), but lengths of stay were similar (13 +/- 5.9 days vs. 12 +/- 7.6 days, P = 0.5). Patients undergoing TT had a higher rate of all wound-healing complications (59% vs. 40%, P = 0.1) and major wound-healing complications (32% vs. 26%, P = 0.6). However, these differences were not statistically significant. No differences in major complications were identified in patients with and without preoperative radiation therapy (26% vs. 28%, P = 0.8). Fifteen per cent (n = 14) of all patients failed to heal wounds at 6 months, but only 9 per cent (n = 2) of patients undergoing TT failed to heal their wounds at 6 months compared with 17 per cent (n = 12) in the non-TT group (P = 0.3). After controlling for important covariates, patients undergoing TT during an APR did not have a significantly lower rate of wound complications. The impact of TT on wound healing in patients with recurrent cancer and preoperative radiation therapy is suggestive of a benefit but requires prospective investigation.

Simplifying the vertical reduction mammaplasty.

The vertical reduction mammaplasty is an evolving technique. Its proponents report significantly decreased scarring, better breast shape, and more stable results compared with the standard inverted-T method, but the learning curve is long and cosmetic outcomes can be inconsistent. Many surgeons have experimented with the vertical closure before returning to methods more familiar to them. The authors present their modifications to the vertical reduction mammaplasty. Their changes simplify the preoperative markings and the intraoperative technique to shorten the learning curve while maintaining reliable aesthetic results. With the patient standing, only four preoperative marks are made: (1) the inframammary fold; (2) the breast axis; (3) the apex of the new nipple-areola complex; and (4) the medial and lateral limbs of the vertical incision. In the operating room, a medial or a superomedial pedicle is developed. Excess breast skin is resected with the inferior and lateral parenchyma as a C-shaped wedge. The lateral skin-adipose flap is redraped inferomedially and sutured to the chest wall. The inferior aspect of the breast is aggressively debulked and a gathering subcuticular stitch is started 2 cm below the nadir of the nipple-areola complex. Finally, a 38-mm to 42-mm nipple-areola complex marker is used to create a circular defect that is offset 0.5 cm medial to the vertical axis of the breast. In their series, 56 patients were treated and no major complications were noted. The median follow-up period was 17 months. The average reduction was 554.5 g per breast; however, the reduction was greater than 1000 g per breast in eight patients. The authors found that (1) chest wall anchoring improves lateral contour and minimizes axillary fullness; (2) aggressive debulking inferiorly avoids the persistent inferior bulge; and (3) starting the subcuticular gathering suture 2 cm below the nipple-areola complex followed by placement of a nipple-areola complex marker at the conclusion of the case prevents lateral deviation and corrects the nipple-areola complex teardrop deformity. These innovations accelerate the learning curve by simplifying the preoperative markings and lead to more consistent postoperative results and an improved cosmetic outcome. In conclusion, these modifications yield a simple, easily learned vertical reduction mammaplasty with aesthetically reliable results.

The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin.

Hypertrophic scarring occurs after deep dermal wounds. Our understanding of the etiology is poor; one reason is the lack of an animal model. In 1972, Silverstein described scarring in the Duroc pig but the model was never confirmed nor disproved. Another reason, as we previously suggested, is that hypertrophic scarring only occurs within regions of human skin that contain cones and the cones have not been studied in relation to hypertrophic scarring. We, therefore (i) explored healing in the female, red Duroc model for similarities to human hypertrophic scarring, studying wound thickness, appearance, healing status at 3 weeks, histology, and immunocytochemical localization of decorin, versican, TGFbeta1 and IGF-1; and (ii) examined Duroc skin for cones. We found that healing after deep wounds in Duroc pigs is similar, but not identical, to human hypertrophic scarring. We also found that Duroc skin contains cones. Healing in the female, red Duroc pig is sufficiently similar to human hypertrophic scarring to warrant further study so that it can be accepted or rejected as a model of human hypertrophic scarring. In addition, the relationship of the cones to hypertrophic scarring needs further detail and can be studied in this model.

Innovations to the vertical reduction mammaplasty: making the transition.

The vertical reduction mammaplasty can be challenging to learn. In addition, first attempts to perform the vertical reduction mammaplasty can lead to inconsistent aesthetic results. The authors describe their transition from a traditional inverted-T reduction mammaplasty to a modified vertical reduction mammaplasty based on a technique described by Elizabeth Hall-Findlay. In their early cases using the Hall-Findlay technique, they noted several aesthetic complications. These problems included a persistent vertical dog-ear deformity at the nadir of the incision, a teardrop deformity of the nipple-areola complex, lateral deviation of the nipple, and lateral axillary fullness. They developed several modifications to the Hall-Findlay technique to correct the aesthetic deficiencies and to simplify further the vertical reduction method. The authors think their innovations facilitate the transition from a traditional inverted-T breast reduction to a successful vertical reduction mammaplasty technique.

Human dermal microvascular endothelial cells produce nerve growth factor: implications for wound repair.

Following cutaneous injury, sensory nerves regenerate into the dermis and epidermis. Tissues that are innervated by sensory nerves synthesize neurotrophins such as nerve growth factor (NGF). The close anatomic proximity of nerves and capillaries throughout the skin suggests that mutual regulation may exist between nerve fibers and microvascular endothelial cells (MECs) during wound repair. Release of the neuropeptide substance P by sensory nerves induces endothelial cell rounding, capillary leak, and cytokine upregulation. We propose that dermal endothelial cells produce neurotrophins required for nerve fiber maintenance and regeneration. In this study, we demonstrate that substance P stimulates NGF messenger RNA expression by cultured human dermal MECs. Likewise, enzyme-linked immunosorbant assay demonstrated that conditioned medium from cultured dermal MECs contains NGF. NGF bioactivity in the supemates was verified by conditioned medium-induced clonal rat pheochromocytoma (PC-12) cell differentiation. This activity was inhibited by anti-NGF antibodies. Therefore, we have demonstrated that substance P, an inflammatory neuropeptide released by sensory nerve fibers, induces endothelial cells to produce NGF. Our data suggest that MECs may be unrecognized contributors to nerve regeneration after cutaneous injury.

Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus.

Background. Patients with diabetic sensory neuropathy have significant risk of chronic ulcers. Insufficient nerve-derived mediators such as substance P (SP) may contribute to the impaired response to injury. Mutant diabetic mice (db/db), which develop neuropathy and have delayed healing, may provide a model to study the role of nerves in cutaneous injury.Methods. Skin from human chronic nonhealing ulcers and age-matched control skin was immunohistochemically evaluated for nerves. Nerve counts were also compared in murine diabetic (C57BL/KsJ-m+/+ Lepr(db); db/db) and nondiabetic (db/-) skin. Excisional wounds on the backs of db/db and db/- mice were grouped as: (a) untreated db/- mice; (b) untreated db/db mice; (c) db/db mice with polyethylene glycol (PEG); (d) db/db mice with PEG and SP 10(-9) M; or (e) db/db mice with PEG and SP 10(-6) M.Results. We demonstrated fewer nerves in the epidermis and papillary dermis of skin from human subjects with diabetes. Likewise, db/db murine skin had significantly fewer epidermal nerves than nondiabetic littermates. We confirmed increased healing times in db/db mice (51.7 days) compared to db/- littermates (19.8 days; P