Localization of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue.

Thrombospondin-1 (TSP-1) is a matrix protein implicated in mechanisms of wound healing. TSP-1 contains the sequence cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) that has been shown to function primarily as a cell adhesion domain. Our laboratory has isolated a novel receptor specific for the CSVTCG adhesive domain of TSP-1. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate TSP-1 and its CSVTCG receptor in surgically created colon anastomotic wounds. Histopathologic and quantitative examination demonstrated increased expression of TSP-1 and its CSVTCG receptor in areas of wound healing. These findings suggest a role for TSP-1 and its CSVTCG receptor in wound healing. The control of expression and activity of these molecules may eventually be the basis for the development of wound healing agents that could significantly reduce the morbidity from surgical intervention.

Histopathology and clinical assessment correlate with the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG) receptor of thrombospondin-1 in breast tumors.

Thrombospondin-1 (TSP-1) is a matrix protein implicated in mechanisms of tumor metastasis. TSP-1 has a characteristic Cysteine-Serine-Valine-Threonine-Cysteine-Glycine (CSVTCG) sequence that functions as a tumor cell adhesion domain. Our laboratory has isolated a novel CSVTCG specific tumor cell receptor. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate the CSVTCG receptor of TSP-1 in a wide spectrum of human archival breast tumors. Histopathologic and quantitative examination was correlated with clinical findings two years post operation. Increasing amounts of CSVTCG receptor correlated positively with worsening histopathologic and clinical findings. These findings suggest a role for the TSP-1 CSVTCG receptor in breast tumor progression. This receptor may have utility for the diagnosis, staging, and treatment of this common and deadly disease.

Inhibition of breast cancer progression by an antibody to a thrombospondin-1 receptor.

BACKGROUND: Thrombospondin-1 (TSP-1) is a matrix-bound adhesive glycoprotein. Breast carcinoma cells exhibit increased expression of a novel TSP-1 receptor. We evaluated the role of this receptor in breast cancer adhesion and progression. METHODS: Adhesion assays were performed to evaluate MDA-MB-231 breast cancer cell adhesion to TSP-1 in vitro in the presence of either nonimmune immunoglobulin G(IgG) or anti-TSP-1 receptor IgG. Receptor-mediated tumor cell progression was evaluated in athymic nude mice. Mice were inoculated with MDA-MB-231 breast cancer cells and randomized to treatment with intraperitoneal injections of saline solution, nonspecific IgG antibody, or an anti-TSP-1 receptor antibody every other day for 20 days. Mice were killed at 21 days. The peritoneal cavity was examined grossly for primary tumor implantation. The liver and lungs were examined histologically for micrometastases. RESULTS: MDA-MB-231 breast cancer cells adhered to TSP-1 in vitro. This adhesion was inhibited to 10% of control by anti-TSP-1 receptor antibody (p < 0.005). Anti-TSP-1 receptor antibody inhibited in vivo breast cancer progression. Mice treated with control IgG antibody or saline solution alone exhibited extensive intraperitoneal seeding. Only one mouse treated with the anti-TSP-1 receptor antibody exhibited any intraperitoneal tumor seeding (p < 0.01). CONCLUSIONS: These data suggest that TSP-1 and its receptor play an important role in breast cancer progression.

Mycobacterium fortuitum infection of the sternum. Review of the literature and case illustration.

Sternal wound infection with atypical mycobacteria following open heart surgery is a rare occurrence. Previous reports have described infection by Mycobacterium fortuitum, an acid-fast bacillus and member of a larger family of rapidly growing mycobacteria. The source and mode of transmission have not been identified. Surgical debridement and the combination of aminoglycosides and quinolones have been shown to be effective methods of treatment. More recently, clarithromycin has been shown to be the drug of choice against rapidly growing mycobacteria. We describe a 49-year-old woman who underwent infundibular stenosis repair and in whom M fortuitum sternal osteomyelitis developed. Total sternectomy, muscle flap reconstruction, and antibiotic treatment successfully eradicated the infection.

Scapular free flap for repair of massive lower facial composite defects.

The scapular osteocutaneous free flap provides excellent tissue for reconstruction of massive lower facial defects. Five cases of full-thickness cheek and lip defects associated with mandibular loss were successfully repaired with sandwiched osteocutaneous scapular flaps plus a parascapular or latissimus dorsi flap. In two instances the osteocutaneous scapular flap was harvested along with a parascapular skin paddle. The other three patients had latissimus dorsi myocutaneous units taken with the scapular osteocutaneous flap from the same subscapular pedicle.

Accuracy of frozen-section diagnosis in salivary gland lesions.

A retrospective study is presented comparing the results of 462 frozen-section analyses of surgically extirpated salivary gland tumors with the permanent-section results. The overall agreement between frozen- and permanent-section analyses was 95.7%. A separate review of the last 47 months of this 32-year study revealed an accuracy rate of 98.8%. Frozen-section diagnosis of salivary gland tumors has been reliable and clinically valuable in our practice.

Lymphoma presenting as a salivary gland mass.

A retrospective review of 36 cases of lymphoma presenting as a salivary gland mass was conducted over a 34-year period. A significant increase in the occurrence of lymphoma was noted in proportion to other salivary gland tumors (P less than 0.01, chi 2 analysis: 1954-1972, 11 of 714 (1.5%); 1973-1979, 9 of 201 (4.5%); 1980-1987, 16 of 265 (6.0%). The mean age was 61 years, sex distribution was equal, and 75% occurred in the parotid. Only 42% presented with signs or symptoms other than a painless mass. Glandular excision was done in early stages of the disease while biopsy was done at later stages. Frozen section analysis was accurate in all but one case and was useful in determining if biopsy were adequate. All patients were definitively treated with chemotherapy and/or radiotherapy. Several instructive points are apparent. Any patient presenting with an isolated salivary gland mass can have a lymphoma. There has, in fact, been a significantly increasing proportion of salivary gland lymphoma among the various salivary gland tumors in our patient population. In contrast to other salivary gland tumors, surgery is reserved for diagnosis and not for treatment. A lymph node biopsy may be sufficient to establish a diagnosis, in which case, glandular excision is unnecessary. Most of the patients presented with an asymptomatic isolated salivary gland mass. The presence of adjacent adenopathy, a rubbery feel to the mass, and the intraoperative appearance were the most suggestive signs of lymphoma. Frozen section analysis is helpful in determining the appropriate extent of surgery and is recommended.

Management of infected laminectomy wounds.

Wound infection after lumbar, thoracic, or cervical laminectomies is a rare but potentially devastating complication. It can range in severity from superficial wound infection to an extensive wound dehiscence. The usual treatment of these wounds consists of intensive local care, debridement, and appropriate antibiotic therapy. Secondary healing can result in chronic, painful wounds that are difficult to manage and can create the potential for osteomyelitis. Seven cases of infected dehiscent laminectomy wounds are presented. Either critical structures were exposed, or the patients did not heal after secondary or delayed primary closures. In each case, full healing was attained by means of reconstruction with a regional muscle flap. We propose that muscle flap reconstruction offers an excellent alternative for the reconstruction of difficult postlaminectomy wounds.

The effect of thrombospondin on oral squamous carcinoma cell invasion of collagen.

BACKGROUND: Thrombospondin (TSP), a cell matrix protein, and transforming growth factor beta (TGF-beta), a growth regulatory protein, play roles in tumor progression. The purpose of this study was to investigate the effects of TSP and TGF-beta on tumor cell invasion. MATERIALS AND METHODS: Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. The KB oral carcinoma cell line was studied in serum-free media. Invasion was measured as the summation of the number of cells in five representative low-power fields (x 100) traversing the collagen barrier after a 3-hour incubation period. The effects of antibodies against TSP, TGF-beta and the cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG)-specific TSP receptor were also evaluated. RESULTS: TSP caused a dose-dependent stimulation of tumor cell invasion. Antibodies against TSP, its CSVTCG-specific receptor, and TGF-beta inhibited TSP-promoted invasion by 50% to 71%. CONCLUSIONS: TSP and its CSVTCG-specific receptor promote KB cell invasion of collagen through the production and/or activation of TGF-beta.

Computer-assisted image analysis of tumor sections for a new thrombospondin receptor.

BACKGROUND: A cell surface receptor (50 kd) has been recently identified in malignant cells that recognizes the tumor cell adhesive domain (ie, cysteine-serine-valine-threonine-cysteine-glycine [CSVTCG]) of thrombospondin (TSP). This CSVTCG-specific TSP receptor can be considered as a new tumor marker, and its concentration on the cell surface may correlate directly with the capacity of tumor cells to invade and metastasize. MATERIALS AND METHODS: Six patients with primary, stages III and IV squamous cell carcinomas of the head and neck were studied. Tumor sections were specifically stained for this receptor with immunohistochemical techniques. The stained specimens were then subjected to computer-assisted image analysis. The area of positive staining and the heterogeneity of the pattern of staining were compared to peritumoral angiogenesis and clinical outcome of the patients. RESULTS: The results indicate that those patients with a high and homogenous positive stain score (mean +/- standard error [SE] 78 +/- 5%) for the CSVTCG-specific TSP receptor had high microvessel density and died from metastatic disease within 12 months of initial treatment (correlation coefficients = 0.95 and 1, respectively). Patients with a low and heterogenous positive stain score for receptor (mean +/- SE 8 +/- 2%; P < 0.001) had low microvessel counts and remained disease-free for at least 2 years. There was no relationship between receptor density and histologic classification of the primary tumors. CONCLUSION: The CSVTCG-specific TSP receptor, quantified through image analysis of immunohistochemical stained tissue sections, is highly predictive of clinical outcome in patients with squamous cell carcinomas of the head and neck.

Wound care in the elderly patient.

Wound care in the elderly population requires careful attention to the medical status of the patient. The patient's underlying medical condition can often dictate what reconstructive options are appropriate. Many reconstructive techniques are available to repair a wide variety of wounds.

Plastic surgery in the elderly.

Plastic surgery has an ever-increasing role in the management of medical problems in the elderly. These procedures can be performed with minimal risk to the patient in order to maximize the quality of life for these patients and their families.

Squamous cell and adnexal carcinomas of the skin.

The diagnosis and treatment of adnexal cancers continues to pose a challenge to a wide range of clinicians. The diseases are a diverse lot, owing to the wide range of skin structures and large surface area. Early recognition and treatment are key to improved outcomes. Education of the patients as to their role in their care, especially early detection, is also of crucial importance. Further study may yield information to improve diagnosis and treatment.

A multidisciplinary approach to wound care in the hospitalized patient.

Wound care services at a tertiary level teaching hospital were reorganized to improve patient care and control costs. A multidisciplinary wound care team was implemented to develop an aggressive, proactive approach to prevent and minimize pressure ulceration. Outcome data demonstrate the efficacy of the wound care team.

Radiation-related wounds of the chest wall.

Irradiation-associated chest wall lesions pose a significant health hazard to the patient. The principles of management include (1) biopsy of any open wounds to rule out the recurrence or persistence of tumor, (2) aggressive debridement of all offending tissues, and (3) reconstruction with well-vascularized flap tissue. Numerous questions arise regarding the practical management of these patients. The controversies that have arisen during our management of more than 100 of these patients have been discussed. It is appropriate to perform reconstruction following nonhealing of a superficial ulcer or immediately following the excision of a full-thickness chest wall defect. Hyperbaric oxygen can serve as a useful adjunct. It is rarely necessary to use a prosthetic material for the purpose of chest wall stabilization during the reconstruction of full-thickness defects. Paradoxic chest wall movement in the postoperative period does not significantly affect pulmonary function tests and is generally a transient problem. Subtotal excisions are frequently necessary. As long as all of the necrotic or tumor-bearing tissue has been fully removed, these wounds can be expected to heal in most instances by placing vascularized tissue into the defect. Operative sites in previously irradiated chest wall tissue can be expected to heal if proper and careful surgical technique is employed. Nevertheless, there is a risk of wound breakdown following any surgery in irradiated tissue. Finally, we believe it is appropriate to proceed with aesthetic recontouring of chest wall deformities associated with irradiation exposure.

Management of radiation-associated pelvic wounds.

Radiation-associated pelvic wounds should be managed by complete excision of all affected tissues and reconstruction with a vascularized flap. The complex anatomy and function of the perineum and pelvis create a variety of reconstructive demands. This article attempts to demonstrate the diversity of the problems that can occur in this region as well as to describe the varied options for reconstruction.

Bipedicle muscle flaps in sternal wound repair.

Infection following median sternotomy is a devastating and potentially life-threatening complication. The use of muscle flaps has become widely accepted as a mainstay in the treatment of these problems. We have previously described our successful use of a bipedicle muscle flap for reconstruction of sternal defects in 16 patients. In this paper, we describe follow-up in those patients as well as an evaluation of this procedure in an additional 26 patients. All records of those patients who had sternal reconstruction using the bipedicle pectoralis major-rectus abdominis flap were reviewed. Factors analyzed included the type of cardiac surgery, associated conditions, complications of surgery, and outcome. There were 42 patients in this group from 1989 to 1996. There were a variety of cardiac procedures represented. Associated conditions included diabetes, chronic hypertension, prolonged postcardiotomy hypotension, prior radiation therapy, pulmonary failure, and steroid use. There were no deaths in this series. There was one flap failure, one persistent infection, one pneumothorax, and one hernia in this series. Three patients developed hematomas after surgery. The most common complication was a skin slough, which occurred in nine patients. This technique provides a large flap that can fill the entire mediastinum. The dissection is rapid, and the complication rate compares favorably to that of other methods.

Outcome assessment of an in-hospital cross-functional wound care team.

A multidisciplinary wound care team was developed at the Medical College of Pennsylvania Hospital in 1993 to standardize wound management, appropriately allocate resources, prevent the occurrence of hospital-acquired decubitus ulcers, and effectively manage existing pressure ulcers. This report presents 4 years of prevalence survey data (n = 690 patients over 4 years), which affords an outcome analysis regarding the efficacy of the multidisciplinary wound care team. A significant reduction in the number of patients with pressure ulcers, hospital acquired pressure ulcers, and patients with hospital acquired ulcers occurred. There was, also, a significant improvement in skin integrity documentation, and in the implementation of nutritional assessments. These findings suggest that the multidisciplinary wound care team has been an effective means of gaining some control of decubitus ulcers, which are associated with increased patient morbidity and have an adverse economic impact on hospitals.

Surgical skin-marking techniques.

Surgical skin-marking inks and dyes are in everyday use for designing and planning incisions in plastic and reconstructive surgery. We have traced the historical development of surgical skin-marking techniques from ancient times to the present. The biochemical characteristics of the commonly used marking agents are discussed. A three-part experiment utilizing a pig model was carried out to test the tissue inflammatory response to the various dyes and inks when used intradermally as tattoos, the persistence of such tattoos, and the ease of skin erasure for each of eight stains. Methylene blue and gentian violet are recommended as the best all-purpose marking agents. The use of proprietary inks is discouraged.