Thermal Therapy of Prostate Tumor Tissue in the Dorsal Skin Flap Chamber

2002 ◽  
Vol 64 (1) ◽  
pp. 170-173 ◽  
Author(s):  
Sankha Bhowmick ◽  
Nathan E. Hoffmann ◽  
John C. Bischof
2001 ◽  
Vol 123 (4) ◽  
pp. 301-309 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
John C. Bischof

Current research in cryosurgery is concerned with finding a thermal history that will definitively destroy tissue. In this study, we measured and predicted the thermal history obtained during freezing and thawing in a cryosurgical model. This thermal history was then compared to the injury observed in the tissue of the same cryosurgical model (reported in companion paper (Hoffmann and Bischof, 2001)). The dorsal skin flap chamber, implanted in the Copenhagen rat, was chosen as the cryosurgical model. Cryosurgery was performed in the chamber on either normal skin or tumor tissue propagated from an AT-1 Dunning rat prostate tumor. The freezing was performed by placing a ∼1 mm diameter liquid-nitrogen-cooled cryoprobe in the center of the chamber and activating it for approximately 1 minute, followed by a passive thaw. This created a 4.2 mm radius iceball. Thermocouples were placed in the tissue around the probe at three locations (r=2, 3, and 3.8 mm from the center of the window) in order to monitor the thermal history produced in the tissue. The conduction error introduced by the presence of the thermocouples was investigated using an in vitro simulation of the in vivo case and found to be <10°C for all cases. The corrected temperature measurements were used to investigate the validity of two models of freezing behavior within the iceball. The first model used to approximate the freezing and thawing behavior within the DSFC was a two-dimensional transient axisymmetric numerical solution using an enthalpy method and incorporating heating due to blood flow. The second model was a one-dimensional radial steady state analytical solution without blood flow. The models used constant thermal properties for the unfrozen region, and temperature-dependent thermal properties for the frozen region. The two-dimensional transient model presented here is one of the first attempts to model both the freezing and thawing of cryosurgery. The ability of the model to calculate freezing appeared to be superior to the ability to calculate thawing. After demonstrating that the two-dimensional model sufficiently captured the freezing and thawing parameters recorded by the thermocouples, it was used to estimate the thermal history throughout the iceball. This model was used as a basis to compare thermal history to injury assessment (reported in companion paper (Hoffmann and Bischof, 2001)).


2001 ◽  
Vol 123 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
John C. Bischof

It has been hypothesized that vascular injury may be an important mechanism of cryosurgical destruction in addition to direct cellular destruction. In this study, we report correlation of tissue and vascular injury after cryosurgery to the temperature history during cryosurgery in an in vivo microvascular preparation. The dorsal skin flap chamber, implanted in the Copenhagen rat, was chosen as the cryosurgical model. Cryosurgery was performed in the chamber on either normal skin or tumor tissue propagated from an AT-1 Dunning rat prostate tumor, as described in a companion paper (Hoffmann and Bischof, 2001). The vasculature was then viewed at 3 and 7 days after cryoinjury under brightfield and FITC-labeled dextran contrast enhancement to assess the vascular injury. The results showed that there was complete destruction of the vasculature in the center of the lesion and a gradual return to normal patency moving radially outward. Histologic examination showed a band of inflammation near the edge of a large necrotic region at both 3 and 7 days after cryosurgery. The area of vascular injury observed with FITC-labeled dextran quantitatively corresponded to the area of necrosis observed in histologic section, and the size of the lesion for tumor and normal tissue was similar at 3 days post cryosurgery. At 7 days after cryosurgery, the lesion was smaller for both tissues, with the normal tissue lesion being much smaller than the tumor tissue lesion. A comparison of experimental injury data to the thermal model validated in a companion paper (Hoffmann and Bischof, 2001) suggested that the minimum temperature required for causing necrosis was −15.6±4.3°C in tumor tissue and −19.0±4.4°C in normal tissue. The other thermal parameters manifested at the edge of the lesion included a cooling rate of ∼28°C/min, 0 hold time, and a ∼9°C/min thawing rate. The conditions at the edge of the lesion are much less severe than the thermal conditions required for direct cellular destruction of AT-1 cells and tissues in vitro. These results are consistent with the hypothesis that vascular-mediated injury is responsible for the majority of injury at the edge of the frozen region in microvascular perfused tissue.


2000 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
Bo H. Chao ◽  
John C. Bischof

Abstract Combination therapies have been investigated as a mean to increase efficacy of disease treatment. For example, combinations such as radiation and chemotherapy, surgery and chemotherapy, and two different chemotherapies have become standard treatment for most cancers. Current theories suggest that vascular-mediated injury is an important mechanism of cryosurgical (reviewed in Gage and Baust (1998)) and hyperthermic destruction (Badylak et al., 1985; Dudar and Jain, 1984) in the treatment of solid tumors. These techniques appear complementary. Freezing creates vascular damage and promotes stasis within the vessels (Rabb et al., 1974), whereas hyperthermia creates cell and vascular destruction more effectively with a compromised vasculature (Shakil et al., 1999). Thus, in this study, we investigated the effect of combining these therapies on the vascular and tissue injury from the two therapies. We chose the dorsal skin flap chamber (DSFC) implanted in the Copenhagen rat as the cryosurgical model for this study. This in vivo freezing model allowed us to monitor thermal history and investigate both vascular and tissue injury in response to the combination therapy.


1993 ◽  
Vol 91 (2) ◽  
pp. 316-321 ◽  
Author(s):  
Dennis C. Hammond ◽  
Ronald D. Brooksher ◽  
Robert J. Mann ◽  
John H. Beernink
Keyword(s):  

2011 ◽  
Vol 26 (4) ◽  
pp. 314-319 ◽  
Author(s):  
Sumara Marques Barral ◽  
Ivana Duval Araujo ◽  
Paula Vieira Teixeira Vidigal ◽  
Cláudio Alvarenga Campos Mayrink ◽  
Adriana Duval Araujo ◽  
...  

PURPOSE: To assess the viability of McFarlane skin flaps in rats with administration of sildenafil. METHODS: Twenty Wistar rats were distributed into two groups: Control (dorsal skin flap, subdermal application of saline solution at 0.9%) and Study (dorsal skin flap, subdermal application of sildenafil). Seven days after the surgery, flaps were photographed and graphically rendered. Then, they were analyzed with AutoCAD software. Three biopsies (proximal, medial and distal) of each flap were collected for histological analysis. RESULTS: Macroscopic analysis showed that animals of the study group had greater necrotic areas (p=0.003) in the dorsal skin flaps. Additionally, histological analysis of the distal third of these flaps showed a tendency to less granulated tissue formation in animals treated with sildenafil. CONCLUSION: Sildenafil subdermally was associated with lower viability of the random skin flap in rats.


1995 ◽  
Vol 154 (4) ◽  
pp. 511-512 ◽  
Author(s):  
L. TÖRKVIST ◽  
U. ÅDÉN ◽  
T. LUNDEBERG ◽  
J. RAUD

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