H. Thomas Temple

A Modified Lodwick-Madewell Grading System for the Evaluation of Lytic Bone Lesions

OBJECTIVE Lodwicks well-established grading system of lytic bone lesions has been widely used in predicting growth rate for lytic bone lesions. We applied a Modified Lodwick-Madewell Grading System as an alternative means to categorize lytic bone tumors into those with low, moderate, and high risks of malignancy. MATERIALS AND METHODS A retrospective review of the radiographs of 183 bone lesions was performed. Cases were selected to include a broad range of benign and malignant tumors. Readers applied our Modified Lodwick-Madewell Grading System, and consensus was reached in all cases. This modified system consists of grade I, which is composed of grades IA and IB as listed in the Lodwick system; grade II, which is grade IC in the Lodwick system; and grade III, which is composed of IIIA (changing margination), IIB (moth-eaten and permeative patterns), and IIIC (radiographically occult). Grading was correlated with the final diagnosis. RESULTS Of the 183 tumors, 81 were classified as grade I, 54 as grade II, and 48 as grade III. When correlating grade with pathology, we found that 76 of 81 (94%) grade I lesions were benign and 39 of 48 grade III lesions (81%) were malignant. A nearly equal number of grade II lesions proved to be benign (29/54; 54%) and malignant (28/54; 53%). CONCLUSION By expanding Lodwicks grading system to include two additional patterns of disease described by Madewell and colleagues (changing margination and radiographically occult) and by reclassifying them into three distinct grades, we propose a modified system-the Modified Lodwick-Madewell Grading System. Application of this system shows correlation of tumor grade with tumor biologic activity and with risk of malignancy: Grade I lesions are usually benign, grade II lesions carry moderate risk of malignancy, and grade III lesions possess a high likelihood of malignancy.

Simulation of biological therapies for degenerated intervertebral discs

The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three‐dimensional finite element model based on a cell‐activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies‐increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)‐to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long‐term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs.

Simulation of water content distributions in degenerated human intervertebral discs.

The objective of this study was to investigate the spatial and temporal variations of water content in intervertebral discs during degeneration and repair processes. We hypothesized that the patterns of water content distribution in the discs are related to the intensity patterns observed in T2‐weighted MRI images. Water content distributions in the mildly (e.g., 80% viable cells in the disc, 2.3% decrease in disc height) and moderately (e.g., 40% viable cells in the disc, 9.3% decrease in disc height) degenerated discs were predicted using a finite element model. The variation of water content in the degenerated discs treated with three biological therapies (i.e., increasing the cell density in the nucleus pulposus [Case I], increasing glycosaminoglycan synthesis rate in the nucleus pulposus [Case II], and decreasing glycosaminoglycan degradation rate in the nucleus pulposus [Case III]) were also predicted. It was found that two patterns of water content distributions, a horizontal region with lower water content at the mid‐axial plane of nucleus pulposus and a spot with higher water content at the posterior region, were shown during the degeneration progress for the disc simulated in this study. These two patterns disappeared after treatment in Case I, but in Case II and Case III. The implication of these patterns for the horizontal gray band and high intensity zone in T2‐weighted MRI images was discussed. This study provided new guidance to develop a novel method for diagnosing disc degeneration and assessing outcomes of biological therapies with MRI techniques.

LHRH receptor expression in sarcomas of bone and soft tissue.

Abstract Aim: Luteinizing hormone releasing hormone (LHRH) is a neurohormone, secreted by the hypothalamus, which regulates the secretion of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary. LHRH acts by binding to receptors located in the pituitary gland. These receptors (LHRH receptors) have also been found in the cytoplasm of many tumor cells that involve both the reproductive and non-reproductive organs. These receptors have been demonstrated in prostate and breast cancers, endometrial carcinomas, renal cell carcinoma, lymphoma, carcinoma of liver, pancreas and skin. So far, the expression of LHRH receptors on sarcomas (i.e. malignant tumors of mesenchymal origin) has not been studied, except for endometrial sarcomas. It has also been demonstrated that both LHRH agonists and antagonists can down-regulate these receptors and thus inhibit these tumor cells. Another major therapeutic implication is that these receptors can be targeted specifically by peptides conjugated to anti-cancer drugs. The purpose of this study was to determine if LHRH receptors are expressed in primary and/or metastatic sarcomas of human origin. Methods: We looked at LHRH receptor expression in 38 consecutive sarcoma specimens, using immunohistochemistry. The specimens were either from office biopsy or from resected tumor; these were confirmed as sarcomas by histopathological examination. The receptor staining characteristics and the staining intensity were also documented. The pattern of staining was classified either as “focal or diffuse staining of the cytoplasm” and the intensity of staining was graded on a scale from 1+ to 4+. Results: Positive receptor staining was seen in 25 of the 38 (66%) specimens. Twelve of the specimens stained diffusely and 13 had focally positive staining. Three tumors had 1+ staining, 10 had 2+ staining, six had 3+ staining, and six tumors had 4+ staining. The tumors included undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, myofibroblastic sarcoma, myxofibrosarcoma, liposarcoma, dermatofibrosarcoma protuberans, metastatic chondrosarcoma and chordoma. Conclusion: Sarcomas express LHRH receptors with a varying incidence and degree. Our study suggests that those sarcomas that are LHRH receptor positive could potentially be treated with targeted chemotherapy.

Orthobiologics in the Foot and Ankle

Many allogeneic biologic materials, by themselves or in combination with cells or cell products, may be transformative in healing or regeneration of musculoskeletal bone and soft tissues. By reconfiguring the size, shape, and methods of tissue preparation to improve deliverability and storage, unique iterations of traditional tissue scaffolds have emerged. These new iterations, combined with new cell technologies, have shaped an exciting platform of regenerative products that are effective and provide a bridge to newer and better methods of providing care for orthopedic foot and ankle patients.

Intravital endoscopic technology for real-time monitoring of inflammation caused in experimental periodontitis

We report a novel method for in situ imaging of microvascular permeability in inflamed gingival tissue, using state-of-the-art Cellvizio™ intravital endoscopic technology and a mouse model of ligature-induced periodontitis. The silk ligature was first placed at the upper left second molar. Seven days later, the ligature was removed, and the animals were intravenously injected with Evans blue. Evans blue dye, which selectively binds to blood albumin, was used to monitor the level of inflammation by monitoring vascular permeability in control non-diseased and ligature-induced experimental periodontitis tissue. More specifically, leakage of Evans blue-bound albumin from the micro-capillary to connective tissue indicates the state of inflammation occurring in the specific site. Evans blue leakage from blood vessels was imaged in situ by directly attaching the endoscope (mini Z tip) of the Cellvizio™ system to the gingival tissue without any surgical incision. Evans blue emission intensity was significantly elevated in gingiva of periodontitis lesions, but not control non-ligature placed gingiva, indicating that this technology can be used as a potential minimally invasive diagnostic tool to monitor the level of inflammation at the periodontal disease site.