Surgery of brain metastases--is there still a place for it?

The role of surgery in the treatment of metastatic brain tumors has always been a source of controversy. It was only in the early 1990s that two randomized prospective trials demonstrated that surgery plus radiation therapy improved survival in patients with single metastatic brain tumors vs. radiation therapy alone. This paper reviews these articles as well as other evidence outlining management options for multiple brain metastases. An attempt has been made to better define the role of surgery in brain metastases. The prognostic factors for brain metastases after surgery are also reviewed and the data comparing stereotactic radiosurgery to surgery is examined. A short description of surgical planning, operative techniques and tools, followed by a discussion on complication avoidance before, during, and after surgery is included.

Biophysical measurement of brain tumor cohesion.

An advantage of using 3D multicellular spheres to study tumor biology is that they better approximate the interactions encountered by cells in vivo. Our previous studies have shown that the process of spheroid formation is governed by the same thermodynamic principles driving the formation of liquid droplets. This liquid-like behavior enables us to measure a key property influencing tumor behavior, namely, intercellular cohesion. We have developed a method, tissue surface tensiometry (TST), to measure the cohesivity, expressible as surface tension (sigma), of tissue aggregates under physiologic conditions. This study utilizes TST to measure the cohesivity of 3 widely used malignant astrocytoma cell lines of different in vitro invasive potentials. We compare invasiveness with aggregate cohesivity and with the expression of N-cadherin, a key mediator of cell-cell cohesion in neural tissues. We show that the cell lines exhibit liquid-like behavior since they form spheroids whose surface tension is both force- and volume-independent; that aggregates from each cell line have a distinct surface tension that correlates with their in vitro invasive capacity; that dexamethasone (Dex), a widely used therapeutic agent for the treatment of tumor-related cerebral edema, increases aggregate cohesivity and decreases invasiveness; that dexamethasone treatment decreases invasion in a dose-dependent manner but only when cells are in direct contact with one another; and that dex-mediated decreased invasiveness correlates with increased aggregate cohesivity as measured by TST but not with N-cadherin expression or function. Our results demonstrate that for these cell lines, cohesivity is an excellent predictor of in vitro invasiveness.