"Analysis of Queueing and Renewal Systems in Hodgkin's Disease".
John H. Frenster, M. D.
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305
Neoplastic diseases such as Hodgkin's Disease consist of a unique interaction of neoplastic cells, immune lymphocytes, phagocytizing macrophages, proliferating blood vessels, collagen-secreting fibroblasts, free tumor antigens, and diffusing antibodies (Natl. Cancer Inst. Monogr. 36: 239 (1973). The complexity of the interaction of these elements suggested the need for new methods of analysis. The techniques of queueing and renewal analysis (Nature 207: 1139 (1965) were applied to involved lymph nodes biopsied at original staging of untreated patients with Hodgkin's Disease. Early analysis revealed a distinct tendency (P<0.01) for neoplastic cells to cluster, with subsequent analyses showing similar tendencies for lymphocytes, macrophages, fibroblasts and endothelium. Within each such cellular cluster, a sequential pattern of cell maturation was observed, indicating queueing within distinct cell renewal systems. Further analysis revealed distinct effects of lymphocyte clusters on neoplastic clusters, and of macrophage clusters on lymphocyte, fibroblast, and endothelial clusters. The possibility of local gradients of free tumor antigen clouds, released from neoplastic clusters, acting as local blocking factors against immune lymphocytes and macrophages was suggested by the data. Thus, queueing and renewal analyses have revealed a non-homogenous distribution of interacting cell populations within Hodgkin's Disease lymph nodes.
2. "Electron Microscopic Analysis of Lymph Node Cellular Activity in Hodgkin's Disease".