Percutaneous Spinal Ablation in a Sheep Model: Protective Capacity of an Intact Cortex, Correlation of Ablation Parameters with Ablation Zone Size, and Correlation of Postablation MRI and Pathologic Findings.

BACKGROUND AND PURPOSE: Despite the growing use of percutaneous ablation therapy for the treatment of metastatic spine disease, several issues have yet to be fully addressed. Our aims were to determine whether the vertebral body cortex protects against ablation-induced spinal cord injury; correlate radiofrequency, cryo-, and microwave ablation parameters with resulting spinal ablation zone dimensions and describe normal spinal marrow postablation changes on MR imaging. MATERIALS AND METHODS: Ten thoracolumbar vertebrae in 3 sheep were treated with radiofrequency ablation, cryoablation, or microwave ablation under fluoroscopic guidance. Technique parameters were chosen to produce ablation zones that exceeded the volume of the vertebral bodies in sheep 1 and were confined to the vertebrae in sheep 2 and 3. Expected ablation zone dimensions were based on data provided by the device manufacturers. Postablation MR imaging was performed at 48 hours (sheep 1) or 7 days (sheep 2 and 3). RESULTS: In sheep 1, cryoablation and microwave ablations extended into the spinal canal and caused histologically confirmed neurologic injury, but radiofrequency ablation did not. The mean difference between the lengths of the radiofrequency ablation zone dimensions measured on gross pathology compared with those expected was 9.6 ± 4.1 mm. The gross pathologic cryo- and microwave ablation zone dimensions were within 1 mm of those expected. All modalities produced a nonenhancing ablation zone with a rim of enhancement, corresponding histologically to marrow necrosis and hemorrhagic congestion. CONCLUSIONS: An intact cortex appears to protect against radiofrequency ablation-induced spinal cord injury, but not against non-impedance-based modalities. Ablation dimensions produced by microwave and cryoablation are similar to those expected, while radiofrequency ablation dimensions are smaller. Ablation of normal marrow produces a rim of enhancement at the margin of the ablation zone on MR imaging.

Remodeling characteristics and biomechanical properties of a crosslinked versus a non-crosslinked porcine dermis scaffolds in a porcine model of ventral hernia repair.

PURPOSE: The objective of this study was to evaluate the histologic remodeling profile and biomechanical properties of the porcine abdominal wall after repair with HDMI-crosslinked (Permacol(®)) or non-crosslinked (Strattice(®)) porcine dermis in a porcine model of ventral hernia repair. METHODS: Bilateral incisional hernias were created in Yucatan minipigs and repaired after 21 days. The repair site, including mesh and abdominal wall, was harvested after 1, 6, and 12 months and subjected to histologic analysis and uniaxial testing. Native abdominal wall without mesh was also subjected to uniaxial tensile testing. RESULTS: Permacol(®) demonstrated significant improvement over time in every remodeling category except scaffold degradation, while remodeling characteristics of Strattice(®) remained relatively unchanged over time for every category except fibrous encapsulation and neovascularization. However, remodeling scores for Strattice(®) were already significantly higher after just 1 month compared to Permacol(®) in the categories of cellular infiltration, ECM deposition, and neovascularization, providing evidence of earlier remodeling of the non-crosslinked grafts compared to the crosslinked grafts. The tensile strength and stiffness of both crosslinked and non-crosslinked graft-tissue composites were greater than the tensile strength and stiffness of the native porcine abdominal wall in the very early post-operative period (1 month), but there was no difference in tensile strength or stiffness by the end of the study period (12 months). CONCLUSIONS: HDMI collagen crosslinking of porcine dermis scaffolds reduces the early histologic remodeling profile but does not significantly impact the tensile strength or stiffness of the graft-tissue composites in a porcine model of ventral hernia repair.

Histologic evaluation of absorbable and non-absorbable barrier coated mesh secured to the peritoneum with fibrin sealant in a New Zealand white rabbit model.

PURPOSE: The purpose of this study is to evaluate the histologic response to fibrin sealant (FS) as an alternative fixation method for laparoscopic ventral hernia repair. METHODS: One non-absorbable barrier mesh (Composix™) and three absorbable barrier meshes (Sepramesh™, Proceed™, and Parietex™ Composite) were used for the study, with uncoated macroporous polypropylene mesh (ProLite Ultra™) as the control. Three methods of fixation were used: #0-polypropylene suture + FS (ARTISS™, Baxter Healthcare Corp.), FS alone (ARTISS™), or tacks alone (n = 10 for each group). Two pieces of mesh (of dimensions 4 × 4-cm) were secured intraperitoneally in 75 New Zealand white rabbits. After 8 weeks, hematoxylin and eosin (H&E)-stained specimens were evaluated for host tissue response. Statistical significance (P < 0.05) was determined using a one-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) post hoc test. RESULTS: Composix™ with FS only showed significantly greater cellular infiltration than with suture + FS (P = 0.0007), Proceed™ with FS only had significantly greater neovascularization than with suture + FS (P = 0.0172), and ProLite Ultra™ with suture + FS had significantly greater neovascularization than with tacks only (P = 0.046). Differences due to mesh type showed that Composix™ exhibited less extensive cellular infiltration (P ≤ 0.0032), extracellular matrix (ECM) deposition, and neovascularization, and demonstrated less inflammatory cells and more fibroblasts compared to the other meshes (P < 0.05). CONCLUSIONS: FS did not have a significant histologic effect compared to tacks when utilized for the fixation of mesh to the peritoneum of New Zealand White rabbits. However, the mesh type did have a significant histologic effect. The permanent barrier mesh (Composix™) was associated with less histologic incorporation than absorbable barrier and macroporous meshes, as evidenced by lower levels of cellular infiltration, ECM deposition, and neovascularization, independent of the fixation method used.

Histologic and biomechanical evaluation of a novel macroporous polytetrafluoroethylene knit mesh compared to lightweight and heavyweight polypropylene mesh in a porcine model of ventral incisional hernia repair.

PURPOSE: To evaluate the biocompatibility of heavyweight polypropylene (HWPP), lightweight polypropylene (LWPP), and monofilament knit polytetrafluoroethylene (mkPTFE) mesh by comparing biomechanics and histologic response at 1, 3, and 5 months in a porcine model of incisional hernia repair. METHODS: Bilateral full-thickness abdominal wall defects measuring 4 cm in length were created in 27 Yucatan minipigs. Twenty-one days after hernia creation, animals underwent bilateral preperitoneal ventral hernia repair with 8 × 10 cm pieces of mesh. Repairs were randomized to Bard(®)Mesh (HWPP, Bard/Davol, http://www.davol.com), ULTRAPRO(®) (LWPP, Ethicon, http://www.ethicon.com), and GORE(®)INFINIT Mesh (mkPTFE, Gore & Associates, http://www.gore.com). Nine animals were sacrificed at each timepoint (1, 3, and 5 months). At harvest, a 3 × 4 cm sample of mesh and incorporated tissue was taken from the center of the implant site and subjected to uniaxial tensile testing at a rate of 0.42 mm/s. The maximum force (N) and tensile strength (N/cm) were measured with a tensiometer, and stiffness (N/mm) was calculated from the slope of the force-versus-displacement curve. Adjacent sections of tissue were stained with hematoxylin and eosin (H&E) and analyzed for inflammation, fibrosis, and tissue ingrowth. Data are reported as mean ± SEM. Statistical significance (P < 0.05) was determined using a two-way ANOVA and Bonferroni post-test. RESULTS: No significant difference in maximum force was detected between meshes at any of the time points (P > 0.05 for all comparisons). However, for each mesh type, the maximum strength at 5 months was significantly lower than that at 1 month (P < 0.05). No significant difference in stiffness was detected between the mesh types or between timepoints (P > 0.05 for all comparisons). No significant differences with regard to inflammation, fibrosis, or tissue ingrowth were detected between mesh types at any time point (P > 0.09 for all comparisons). However, over time, inflammation decreased significantly for all mesh types (P < 0.001) and tissue ingrowth reached a slight peak between 1 and 3 months (P = 0.001) but did not significantly change thereafter (P > 0.09). CONCLUSIONS: The maximum tensile strength of mesh in the abdominal wall decreased over time for HWPP, LWPP, and mkPTFE mesh materials alike. This trend may actually reflect inability to adequately grip specimens at later time points rather than any mesh-specific trend. Histologically, inflammation decreased with time (P = 0.000), and tissue ingrowth increased (P = 0.019) for all meshes. No specific trends were observed between the polypropylene meshes and the monofilament knit PTFE, suggesting that this novel construction may be a suitable alternative to existing polypropylene meshes.

Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

PURPOSE: Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. METHODS: Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. RESULTS: There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. CONCLUSIONS: While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

Evaluation of fenestrated and non-fenestrated biologic grafts in a porcine model of mature ventral incisional hernia repair.

INTRODUCTION: The purpose of this study is to compare the tissue incorporation of a novel fenestrated and non-fenestrated crosslinked porcine dermal matrix (CPDM) (CollaMend™, Davol Inc., Warwick, RI) in a porcine model of ventral hernia repair. METHODS: Bilateral abdominal wall defects were created in 12 Yucatan minipigs and repaired with a preperitoneal or intraperitoneal technique 21 days after hernia creation. Animals were randomized to fenestrated or non-fenestrated CPDM for n = 6 pieces of each graft in the preperitoneal or intraperitoneal location. All animals were sacrificed at 1 month. Adhesion characteristics and graft contraction/growth were measured by the Garrard adhesion grading scale and transparent grid overlay. Histological analysis of hematoxylin and eosin (H&E)-stained slides was performed to assess graft incorporation. Tissue incorporation strength was measured by a T-peel tensile test. The strength of explanted CPDM alone and de novo CPDM was measured by a uniaxial tensile test using a tensiometer (Instron, Norwood, MA) at a displacement rate of 0.42 mm/s. Statistical significance (P < 0.05) was determined for histological analysis using a Kruskal-Wallis non-parametric test with a Bonferroni correction, and for all other analyses using a two-way analysis of variance (ANOVA) with a Bonferroni post-test or a Kruskal-Wallis non-parametric test with a Dunn's post-test. RESULTS: Intraperitoneal placement of fenestrated CPDM resulted in a significantly higher area of adhesions and adhesion score compared to the preperitoneal placement of fenestrated CPDM (P < 0.05). For both preperitoneal and intraperitoneal placement, histological findings demonstrated greater incorporation of the graft due to the fenestrations. No significant differences were detected in the uniaxial tensile strengths of the graft materials alone, either due to the graft type (non-fenestrated vs. fenestrated) or due to the placement location (preperitoneal vs. intraperitoneal). The incorporation strength (T-peel force) was significantly greater for fenestrated compared to non-fenestrated CPDM when placed in the preperitoneal location (P < 0.01). The incorporation strength was also significantly greater for fenestrated CPDM placed in the preperitoneal location compared to fenestrated CPDM placed in the intraperitoneal location (P < 0.05). CONCLUSIONS: Fenestrations in CPDM result in greater tissue incorporation strength and lower adhesion area and score when placed in the preperitoneal location. Fenestrations in CPDM allow for greater tissue incorporation without accelerating graft degradation. Fenestrations may be placed in CPDM while still allowing adequate graft strength for intraperitoneal and preperitoneal hernia repairs at 1 month in a porcine model.

Use of intraosseous blood for repeated hematologic and biochemical analyses in healthy pigs.

OBJECTIVE: To evaluate the clinical and histologic effects of repeated intraosseous (IO) needle placement in domestic pigs and determine whether blood and serum obtained intraosseously could be used for CBC and biochemical analyses. ANIMALS: 5 healthy 10-week-old pigs. PROCEDURE: An IO needle was placed in the proximomedial region of the tibia of anesthetized pigs every other week for 2 months, and IO blood was obtained for CBC and serum biochemical analyses. Results were compared with those obtained for blood collected at the same time from the auricular vein. Two weeks after the final samples were obtained, pigs were euthanatized and tibias were processed for histologic examination. RESULTS: Clinical abnormalities, including lameness, were not detected following IO needle placement. Histologic examination revealed only mild multifocal periosteal fibrosis and slight thickening of the periosteum without evidence of osteomyelitis. Chloride, creatinine, glucose, total protein, sodium, and BUN concentrations, alanine transaminase and gamma glutamyl transpeptidase activities, RBC count, mean corpuscular volume, and Hct did not significantly differ between IO and venous samples. However, aspartate transaminase activity, potassium, hemoglobin, and mean corpuscular hemoglobin concentrations, mean corpuscular hemoglobin, and platelet and WBC counts were significantly different. CONCLUSION AND CLINICAL RELEVANCE: Repeated placement of 10 needles may be a safe and clinically useful method to obtain serial blood samples from domestic pigs, particularly when other vascular sites are not accessible. Intraosseous blood can be used for many of the tests comprising CBC and serum biochemical analyses.

The effect of propofol administered intravenously on appetite stimulation in dogs.

Anorexia is defined as diminished appetite or aversion to food. Clinical manifestations of anorexia have multiple etiologies, which include systemic illness, pain, fever, stress, metabolic disorders, and decreased palatability and learned aversion to food. Disorders of appetite are common in companion and laboratory animal medicine. Anecdotal evidence and personal experience suggest that propofol (2, 6-diisopropylphenol), when given intravenously at subhypnotic doses, causes acute appetite stimulation in dogs. The establishment of a dose-response effect could have important clinical applications; therefore, this study attempts to qualify and quantify the effect of propofol on appetite stimulation in healthy young adult dogs. Six purpose-bred male dogs (age, 6 months) were obtained from a Class A vendor. Dogs were housed individually and provided water ad libitum throughout the study period. All dogs were fed ad libitum to ensure that test conditions and degree of satiety were identical. Each dog was assigned randomly to either an experimental group or control each day of the study. The experimental groups received single bolus intravenous injections of propofol at different dosage levels (0.5, 1.0, 1.5, 2.0, or 3.0 mg/kg of body weight), and the control group received saline. The administrator was blinded to the animals identification and dose. Dosages greater than 3.0 mg/kg resulted in profound sedation and ataxia, which physically inhibited the dogs from obtaining the food; therefore 3.0 mg/kg was the highest dose tested. Dogs were weighed daily to ensure accurate dosing. Dosing was performed at the same time each day to minimize variability. Food intake amounts were recorded at 15, 30, 60, 120, and 1440 min after injection. Food intake was expressed as [food intake (g)/ body weight (kg)/ unit time (min)]. After a 1-w rest period, the study was repeated. Data were analyzed with a type RBF-65 randomized-block factoral design (ANOVA). Each dog served as its own control. The two experiments were analyzed separately, and a P-value of less than 0.05 was used to declare statistical significance. A significant (P, 0.05) increase in food consumption was observed solely during the 0-to-15-min time interval; no significant increase in food consumption was observed at any other time point. This data supports propofols appetite stimulating effect in the initial 15 min after injection. Additional studies are required to explore the mechanism for this effect and to determine whether it occurs in other species.

Intensity-modulated radiotherapy: first results with this new technology on neoplasms of the head and neck.

Intensity-modulated beam radiotherapy (IMRT) delivers a highly conformal, three-dimensional (3-D) distribution of radiation doses that is not possible with conventional methods. When administered to patients with head and neck tumors, IMRT allows for the treatment of multiple targets with different doses, while simultaneously minimizing radiation to uninvolved critical structures such as the parotid glands, optic chiasm, and mandible. With 3-D computerized dose optimization, IMRT is a vast improvement over the customary trial-and-error method of treatment planning. We retrospectively reviewed the charts of the first 28 head and neck patients at our institution who were treated with IMRT. All had head and neck neoplasms, including squamous cell carcinoma, adenoid cystic carcinoma, paraganglioma, and angiofibroma. Total radiation doses ranged from 1,400 to 7,100 cGy, and daily doses ranged from 150 to 400 cGy/day. A quality assurance system ensured that computer-generated dosimetry matched film dosimetry in all cases. For midline tumors, this system allowed us to decrease the dose to the parotid glands to less than 3,000 cGy. The incidence of acute toxicity was drastically lower than that seen with conventional radiotherapy delivery to similar sites. This is the first report of the application of IMRT strictly to head and neck neoplasms. We discuss the indications, technique, and initial results of this promising new technology. We also introduce the concept of the Simultaneous Modulated Accelerated Radiation Therapy boost technique, which has several advantages over other altered fractionation schemes.