Cryosurgery of Normal and Tumor Tissue in the Dorsal Skin Flap Chamber: Part II—Injury Response

2001 ◽  
Vol 123 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
John C. Bischof
Keyword(s):  
Vascular Injury ◽  
Normal Tissue ◽  
Tumor Tissue ◽  
Skin Flap ◽  
Hold Time ◽  
Companion Paper ◽  
Temperature History ◽  
Dorsal Skin ◽  
Tissue Lesion ◽  
Cellular Destruction

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.

Cryosurgery of Normal and Tumor Tissue in the Dorsal Skin Flap Chamber: Part I—Thermal Response

2001 ◽  
Vol 123 (4) ◽  
pp. 301-309 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
John C. Bischof
Keyword(s):  
Blood Flow ◽  
Thermal Properties ◽  
Thermal History ◽  
Tumor Tissue ◽  
Normal Skin ◽  
Skin Flap ◽  
Companion Paper ◽  
Two Dimensional ◽  
Dorsal Skin ◽  
Freezing And Thawing

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)).

Observation of Vascular Injury After Freezing: Investigating the Response of Normal Skin and Subcutaneous AT-1 Tumor Tissue to Cryosurgery in the Dorsal Skin Flap Chamber

1999 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
David J. Swanlund ◽  
John C. Bischof
Keyword(s):  
Vascular Injury ◽  
Thermal History ◽  
Host Response ◽  
Tissue Injury ◽  
Skin Flap ◽  
Tissue Type ◽  
Crystal Formation ◽  
Dorsal Skin ◽  
Tissue Necrosis

Abstract Two main mechanisms have been explored in an attempt to explain injury to the cells of tissues due to freezing in vivo. The first is direct cellular injury caused by injurious osmotic changes and ice crystal formation that happens as a result of freezing (Mazur, 1984). The second is host response injury caused by the vascular damage and immunologic response in response to freezing (Gage and Baust, 1998). The amount of injury caused by freezing appears to vary with tissue type and thermal history of the freezing protocol. The hypothesis of this study was that host response injury, specifically vascular injury, causes the majority of tissue necrosis at the edge of a frozen region and therefore determines the size of the lesion seen after in vivo freezing. Many investigations have previously made a qualitative correlation between thermal history, vascular injury, and tissue necrosis (e.g. Greene. 1943 and Rabb et al., 1974). 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 appears insensitive to the immunologic phenomenon (Hoffmann et al., 1999) and allows us to monitor thermal history and investigate both vascular and tissue injury in response to cryosurgery.

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
Keyword(s):  
Tumor Tissue ◽  
Skin Flap ◽  
Prostate Tumor ◽  
Thermal Therapy ◽  
Dorsal Skin

APPLICATION OF PIXE TO CANCER RESEARCH

1992 ◽  
Vol 02 (04) ◽  
pp. 529-534 ◽  
Author(s):  
HUIYING YAO ◽  
XIANZHOU ZENG ◽  
JIYAO CHEN ◽  
WEN CHEN ◽  
HUAIXIN CAI ◽  
...  
Keyword(s):  
Cancer Research ◽  
Trace Elements ◽  
Photodynamic Therapy ◽  
Normal Tissue ◽  
Second Generation ◽  
Tumor Tissue ◽  
Photodynamic Effect ◽  
Malignant Tumours ◽  
Local Destruction

Photodynamic therapy (PDT) is a promising approach to the local destruction of malignant tumours. This method is based on the partially selective retension in tumor tissue of the photosensitizers which have photodynamic effect. It is important for PDT to determine the photosentizer concentration in tumor and in normal tissue. We quantitatively analysed the concentration of the metallic phthalocyanines, a class of photosensitizers now recognized as “second generation” PDT drugs and studied its action in different time by PIXE technique. The paper shows also the correlation between trace elements and cancer.

Cryo, Hyper or Both? Investigating Combination Cryo/Hyperthermia in the Dorsal Skin Flap Chamber

2000 ◽  
Author(s):  
Nathan E. Hoffmann ◽  
Bo H. Chao ◽  
John C. Bischof
Keyword(s):  
Combination Therapy ◽  
Thermal History ◽  
Standard Treatment ◽  
Tissue Injury ◽  
Skin Flap ◽  
Dorsal Skin ◽  
Combination Therapies ◽  
Disease Treatment ◽  
Copenhagen Rat

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.

The Dorsal Skin-Flap Model in the Rat

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

scholarly journals Effects of sildenafil on the viability of random skin flaps

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 ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Histological Analysis ◽  
Saline Solution ◽  
Skin Flap ◽  
Study Group ◽  
Tissue Formation ◽  
Skin Flaps ◽  
Dorsal Skin ◽  
Macroscopic Analysis

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.

scholarly journals Expression of miRNA and Occurrence of Distant Metastases in Patients with Hürthle Cell Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Rok Petric ◽  
Barbara Gazic ◽  
Katja Goricar ◽  
Vita Dolzan ◽  
Radan Dzodic ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Metastatic Disease ◽  
Normal Tissue ◽  
Tumor Tissue ◽  
Thyroid Tissue ◽  
Distant Metastases ◽  
Rare Type ◽  
Hürthle Cell ◽  
U6 Snrna ◽  
Ffpe Samples

Background. Hürthle cell thyroid carcinoma (HCTC) is a rare type of thyroid carcinoma. In the present study, we investigated whether the expression of miRNAs of interest is associated with the occurrence of metastases in patients with HCTC.Materials and Methods. In 39 patients with HCTC (22 with nonmetastatic and 17 with regional or distant metastatic disease), the expression levels of six miRNAs (miR-138, miR-183, miR-221, miR-222, miR-768-3p, and miR-885-5p) and U6 snRNA as endogenous control were determined in FFPE samples of primary tumor and normal thyroid tissue using TaqMan miRNA assays.Results. In patients with HCTC, miR-138 and miR-768-3p were downregulated in tumor samples compared to normal tissue (p=0.013andp=0.010, resp.). These two miRNAs were also significantly downregulated in tumor samples of patients with metastatic disease (p=0.030andp=0.048, resp.) but not in patients with nonmetastatic disease (p=0.249andp=0.101, resp.). In patients with nonmetastatic disease, miR-221 and miR-885-5p were slightly, albeit significantly, upregulated in tumorous compared to normal tissue (p=0.042andp=0.027, resp.).Conclusion. Expression of miRNA (miR-183, miR-221, and miR-885-5p) in tumor tissue is associated with the occurrence of distant metastases in patients with HCTC.

Sign in / Sign up

Export Citation Format

Share Document