Baust J.G.,Binghamton University State University of New York |
Gage A.A.,State University of New York at Buffalo |
Bjerklund Johansen T.E.,University of Oslo |
Baust J.M.,CPSI Biotech
Cryobiology | Year: 2014
While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer, which while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer. © 2013 Elsevier Inc.
Robilotto A.T.,Binghamton University State University of New York |
Baust J.M.,Binghamton University State University of New York |
Van Buskirk R.G.,Binghamton University State University of New York |
Gage A.A.,CPSI Biotech |
And 2 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2013
Background:Critical to the continual improvement of cryoablation efficacy is deciphering the biochemical responses of cells to low-temperature exposure. The identification of delayed-onset cell death has allowed for the manipulation of cellular responses through the regulation of apoptosis. We hypothesized that in addition to delayed apoptotic events associated with mild subfreezing temperatures (10 to -25 °C), cells exposed to ultra-low temperatures (<-30 °C) may undergo rapid, early-onset apoptosis.Methods:Human prostate cancer model and cells (PC-3) were exposed to temperatures of -60, -30 and -15 °C to simulate a cryoablative procedure. Using a combination of flow-cytometry, fluorescent microscopy and western blot analyses, samples were assessed at various times post thaw to identify the presence, levels and the pathways involved in cell death.Results:Exposure to temperatures <-30 °C yielded a significant apoptotic population within 30 min of thawing, peaking at 90 min (∼40%), and by 6 h, only necrosis was observed. In samples only reaching temperatures >-30 °C, apoptosis was not noted until 6-24 h post thaw, with the levels of apoptosis reaching ∼10% (-15 °C) and ∼25% (-30 °C) at 6 h post thaw. Further, it was found that early-onset apoptosis progressed through a membrane-mediated mechanism, whereas delayed apoptosis progressed through a mitochondrial path.Conclusions:These data demonstrate the impact of apoptotic continuum, whereby the more severe cryogenic stress activated the extrinsic, membrane-regulated pathway, whereas less severe freezing activated the intrinsic, mitochondrial-mediated path. The rapid induction and progression of apoptosis at ultra-low temperatures provides an explanation as to why such results have not previously been identified following freezing. Ultimately, an understanding of the events and signaling pathways involved in triggering apoptosis following freezing may provide a path for selective induction of the rapid-onset and delayed programmed cell death pathways in an effort to improve the overall cryoablation efficacy. © 2013 Macmillan Publishers Limited. All rights reserved.
Cpsi Biotech | Date: 2011-03-17
An embodiment of the invention is a cryo-connector, a connector that allows for the delivery and return of a cryogen in an axial configuration. In one embodiment, the connector is a tri-axial configuration allowing for the delivery and return of pressurized cryogen as well as the application of an independent vacuum in the third lumen. Various configurations, however, may accommodate any number of luminary spaces such that cryogen (or other fluids) and/or vacuum spaces may be created in a fashion complementary to the components that the connector will affix to and interconnect with. The connectors can be utilized with any low temperature, cryogenic device and at varying pressures.
Cpsi Biotech | Date: 2011-02-15
A cryogenic medical device is disclosed for use in minimally invasive surgical procedures. Various configurations of cryoprobes are designed in combination with a clamp to form a cryoclamp for the treatment of damaged, diseased, cancerous or other unwanted tissues. The device is an integrated cryoablation probe with a hinged clamp that allows for single entry into the chest cavity through a thorascopic port, by surgical or other means. The integrated cryoablation probe allows for the clamping of tissue as well as freezing with a single device. The clamp acts as an outer sheath so that when closed, directional freezing of the cryoprobe is achieved on the opposing probe surface away from the clamp or on an internal surface that is between the clamp. The cryoclamp may be a removable attachment or integrated into the unitary device.
Cpsi Biotech | Date: 2011-03-31
One embodiment of the invention is a flexible cryogenic probe tip. The flexible probe tip has a linear freeze zone at a distal end of the probe that allows for its placement and precisely controlled movements. The flexible cryogenic probe tip precisely conforms to the target tissue surface to create a linear lesion. In addition, the probe tip is steerable to facilitate proper placement with minimal access points into a patients body. Various configurations of the flexible probe tip allow it to conform and ablate tissue of many sizes, shapes, and/or dimensions. Methods of utilizing the cryogenic probe tip include steps of positioning the distal end at a tissue site for at least one ablative procedure, maneuvering the distal end to the tissue site, directing a cryogen from the supply source to the distal end, controlling a flow of cryogen from the supply source to the distal end and back to the supply source, and segmenting control of the distal end mechanically or through the step of controlling the flow of cryogen.