Mark P. Solomon

The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck.

Tumor angiogenesis has recently been related to tumor growth and metastasis, which determine the clinical outcome of the patient. This study was designed to determine the relationship between angiogenesis in primary squamous cell carcinomas (SSC) of the head and neck and the development of recurrent or metastatic disease, or both. Different SCC of the head and neck were studied. Microvessels were selectively stained using a monoclonal antibody for factor VIII. Microvessel counts were performed in the tumor, in the tissues immediately adjacent, and in normal tissues of similar topographies. Microvessel counts were then correlated with clinical outcome (development of recurrent or metastatic disease, or both). Recurrent or metastatic disease, or both, developed in patients with high microvessel counts (mean, 121.25) in the tissues adjacent to the tumor 7 to 16 months after initial treatment. Those with low microvessel counts (mean, 33.75) were disease-free for 16 months to 6 years (p < 0.01). Microvessel counts inside the tumor were also higher in those in whom recurrences or metastasis, or both, developed, but were not statistically significant. In this study, angiogenesis was directly related to clinical outcome. Thus, angiogenesis may be an independent predictor of recurrent or metastatic disease, or both, which could help in the selection of patients with SCC of the head and neck for aggressive therapy.

Experience with the Furlow double-reversing Z-plasty for cleft palate repair.

One-hundred and six cases of soft palate closure using the Furlow double-reversing Z-plasty technique have been reported. Most of these patients have been done in the past 2 years. There seem to be a number of worthwhile advantages to this procedure, with few disadvantages or complications. The operation is adaptable for use in early soft palate closure (3 to 6 months) as well as late closure (12 to 14 months), in submucosal clefts, as well as in secondary palatal repair where lengthening and repositioning of the levator muscle is desired. With this type of palatoplasty, the need for raising or shifting large mucoperiosteal flaps from the hard palate has been completely avoided. The operation can be combined with a primary posterior pharyngeal flap if desired, although this is not advised if early palatal closure (3 to 6 months) is used because of a high incidence of sleep apnea. Preliminary speech results are very encouraging.

Bipedicle muscle flaps in sternal wound repair.

&NA; 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. (Plast. Reconstr. Surg. 101: 356, 1998.)

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.

Hair removal using the long-pulsed ruby laser.

There are a variety of traditional treatments for the removal of unwanted hair. Recently, lasers have been developed to remove hair. The long-pulsed ruby laser uses light at a wavelength of 694 nm with a 3-msec pulse to destroy hair. Seventy-two patients were treated with this laser from one to four times in a variety of areas. Seventy-one patients had an alteration in their hair growth. One patient had no change in her hair pattern. There were no scars and no permanent changes in pigmentation. Laser hair removal is a useful method for the treatment of unwanted facial and body hair.

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.

Modulation of Cranial Bone Healing with a Heparin-like Dextran Derivative

Substituted dextran polymers have been shown to bind growth factors and protect them from enzymatic degradation. Using this information, other researchers have been able to use these substituted dextrans to enhance the healing of bone in an environment where bone would otherwise not regenerate. We used substituted dextran polymers to evaluate their ability to accelerate the healing of cranial bone in a rabbit model. We were able to document a more rapid rate of healing and demonstrate micrographic evidence to support that conclusion. Possible mechanisms are postulated.

Surgical Management of Radiated Scalp in Patients with Recurrent Glioma

Patients with malignant brain tumors requiring multiple craniotomies and external beam radiotherapy are at risk of scalp wound breakdown secondary to fibrosis and radiation damage. We present three cases to illustrate the nature of the problem and the surgical approaches to scalp repair. When a bicoronal incision has been used for the initial craniotomy, the plastic repair can be performed with a bipedicle visor scalp flap and split-thickness skin graft to cover the pericranium at the donor site. When a curvilinear (U-shaped or horseshoe) flap has been used for the initial craniotomy, a single-pedicle flap may be rotated to achieve closure without tension. In anticipation of the risk of scalp wound breakdown in patients with malignant brain tumors, the planning of the operative incision for the first craniotomy needs to take into account the long-term viability of the scalp. We recommend linear scalp incisions parallel to the arterial distribution instead of the traditional curvilinear (U-shaped or horseshoe) flaps; linear incisions are less likely to break down, and in the event of breakdown, linear wounds offer better therapeutic surgical options for plastic repair.

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.

Reconstruction of radiation-induced chest wall lesions

Radiation-related ulcers of the chest wall provide a great challenge to reconstructive surgeons because of the necessity of protecting the underlying vital structures and the difficulty in repairing irradiated tissues. To evaluate the efficacy of treatment, 24 patients who underwent reconstruction of radiation related ulcers of the chest wall were retrospectively reviewed. A variety of muscle and musculocutaneous flaps as well as omentum and microvascular tissue transfers were used to reconstruct these defects. The defects in the chest wall arose from spontaneous breakdown of irradiated tissue, tumor recurrence, or nonhealing after surgical procedures performed in the irradiated field. Our treatment protocol consisted of aggressive debridement of all affected tissues including skeletal tissues when necessary. The application of a tension free closure using a flap was then performed. Skeletal support was provided in three reconstructions. There were no mortalities, the morbidity rate was 29% (six minor, one major complication), and the mean hospital stay was 10.9 days. None of the patients required prolonged ventilator support. In all but 2 patients, who were left with small chronic granulating nonhealing wounds, complete wound healing was achieved. We conclude that chest wall reconstruction of radiation-related ulcers can be achieved with minimal morbidity in an acceptable period of inpatient hospital care using a variety of vascularized tissue transfers.