Thomas A. Mustoe

Primary intraosseous carcinoma of the mandible with probable origin in an odontogenic cyst

Primary intraosseous carcinoma of the jaws (PIOC) is an uncommon lesion, but may not be as rare as commonly believed. Since the putative source of the epithelium giving rise to an intraosseous carcinoma is the epithelium involved in odontogenesis, these lesions are often designated as odontogenic carcinomas. These tumors may theoretically arise (1) from the lining of odontogenic cysts, (2) from other epithelial odontogenic tumors, or (3) de novo from presumed odontogenic rests. While not included in most classifications of PIOC, it appears logical to also include intraosseous mucoepidermoid carcinomas as a fourth type of PIOC. A case of primary intraosseous squamous cell carcinoma of the mandible, with evidence of origin in an odontogenic cyst, is presented. The recent literature on carcinomas arising in jaw cysts is reviewed.

Current concepts in wound healing: growth factor and macrophage interaction.

Growth factors are potent wound healing promoters which accelerate incisional wound repair by distinct mechanisms. Transforming growth factor-beta (TGF-beta), a chemotactic factor, increases synthesis of extracellular matrix and stimulates granulation tissue. We demonstrated that a single topical dose of TGF-beta increased the wound breaking strength in normal models of tissue repair as well as in models of impaired wound repair, characterized by severe monocytopenia. PDGF, a chemotactic agent for inflammatory cells, with mitogenic activity, activates monocytes and stimulates collagen production, significantly increased the wound breaking strength with effects that lasted for up to 47 days. In contrast to TGF-beta, PDGF was only active in normal models of wound healing and its effects were dependent upon the presence of macrophages. PAF is a glycerophospholipid which chemotaxes and activates macrophages, but differs from growth factors in lacking mitogenic activity. A single topical dose of PAF significantly increased the wound breaking strength and promoted macrophage migration.

Enhancement of Wound Healing by the Alkaloid Taspine Defining Mechanism of Action

Abstract Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 μg, but not those treated with 50 μg or 10 μg, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 μg had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.

Transforming Growth Factor‐β Effect on Soft Tissue Repair

Previous studies have demonstrated that TGF-beta possesses many of the biologic properties necessary for acceleration of the normal wound healing process. We report that recombinant human TGF-beta 2 (rhuTGF-beta 1) increases wound strength and accelerates wound closure when applied topically to experimental wounds. Doses of 5 to 1,000 ng/wound increased wound strength in a dose-response manner and wound strength increase as high as 161% above control in the rat incisional wound model. Increased wound strength was observed as early as 3 days following rhuTGF-beta 1 application and continued to Day 28. In the rabbit ear ulcer model, acceleration of wound closure was observed following doses of 5 to 100 ng/wound applied a single topical application. No adverse effects of rhuTGF-beta 1 were observed. The amount of fibrous tissue, scar formation, and mitotic figures were not significantly greater than control. Epithelialization of rhuTGF-beta 1-treated wounds was not impeded. rhuTGF-beta 1 induced bone formation in the rabbit ear ulcer model but not in the rat incisional model, suggesting that precursor cells, such as perichondrial cells, are required for the bone forming activities of TGF-beta 1.

Carcinoma in chronic pressure sores: a fulminant disease process.

Four cases of squamous cell carcinoma arising chronic pressure sores in paraplegic and tetraplegl tients are presented and the literature reviewed. T pressure-sore carcinomas are characterized by a shi latency period and a fulminant clinical course with a high metastatic rate. Very aggressive treatment inclu even hemicorporectomy must be considered if a CL to be achieved.

Acceleration of soft tissue repair by a thrombin-derived oligopeptide

Augmentation of thrombin-modulated chemotaxis and mitogenic activity within the early phase of soft tissue repair is now possible. Identification of high-affinity thrombin receptor binding domains within thrombin has enabled the synthesis of a family of peptides which interact with thrombin receptors and enhance in vitro mitogenesis. A single (5.0 micrograms/wound) application of the thrombin receptor-activating peptide (P517-30) significantly increased wound breaking strength from Day 5 (31% over controls) to Day 12. Two models of impaired healing created by radiotherapy (RT) were used to elucidate possible mechanisms of P517-30 action. Although P517-30 did not completely overcome the RT-induced healing impairments, it increased breaking strength under conditions of penetrating whole body RT-induced pancytopenia by 22% and of nonpenetrating surface RT-induced dermal cell damage by 42%. This suggests that P517-30 directly stimulates resident endothelial cells, fibroblasts, or other cells to overcome dermal and circulating monocytic deficits. These results suggest a method to accelerate wound healing with potential clinical applications and emphasize the activity of thrombin as a growth factor.

The frontonasal flap: utility for lateral nasal defects and technical refinements

This report details the experience with 27 patients over a 5-year period who had nasal reconstruction using a frontonasal flap. The frontonasal flap procedure is a useful method for the repair of relatively large post-Mohs micrographic surgery defects of the lower, upper, lateral and central nose. Our modified method has been extended (1) to resurface lateral as well as central defects of the caudal one-third of the nose; (2) the scar can be shortened so it does not extend into the forehead; (3) the flap can be combined with the island nasalis flap, or nasolabial flaps to resurface large (3-4 cm) defects; (4) early dermabrasion has improved the scars in sebaceous skin.

Lymph node metastasis in spindle cell carcinoma arising in odontogenic cyst. Report of a case.

The majority of primary intraosseous carcinomas of the jaws develop in preexisting odontogenic cysts. These tumors are usually well-differentiated keratinizing carcinomas with relatively good prognosis. Only two of 41 previously reported acceptable cases of primary intraosseous carcinomas from ex-odontogenic cysts were associated with cervical lymph node metastasis. Spindle cell carcinoma is an anaplastic dimorphic neoplasm with poor prognosis. It has a special predilection for the upper aerodigestive tract. This is to our knowledge the first report of spindle cell carcinoma developing in an odontogenic cyst. Cervical lymph node metastasis showing typical histologic features of spindle cell carcinoma was detected 8 months postoperatively. The prognostic implications of this finding are discussed in light of previously reported cases of intraosseous carcinoma arising in odontogenic cysts and of spindle cell carcinoma of the oral cavity.