A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields.

Strategies for treating liver cancer using radiation, chemotherapy combinations and tyrosine kinase inhibitors targeting specific mutations have provided longer survival times, yet multiple treatments are often needed and recurrences with new malignant phenotypes are not uncommon. New and innovative treatments are undoubtedly needed to successfully treat liver cancer. Over the last decade, nanosecond pulsed electric fields (nsPEFs) have shown promise in pre-clinical studies; however, these have been limited to treatment of skin cancers or xenographs in mice. In the present report, an orthotopic hepatocellular carcinoma (HCC) model is established in rats using N1-S1 HCC cells. Data demonstrate a response rate of 80-90% when 1000 pulses are delivered with 100ns durations, electric field strengths of 50kV/cm and repetition rates of 1Hz. N1-S1 tumours treated with nsPEFs expressed significant number of cells with active caspase-3 and caspase-9, but not caspase-8, indicating an intrinsic apoptosis mechanism(s) as well as caspase-independent mechanisms. Most remarkably, rats with successfully ablated tumours failed to re-grow tumours when challenged with a second injection of N1-S1 cells when implanted in the same or different liver lobe that harboured the original tumour. Given this protective effect, infiltration of immune cells and the presence of granzyme B expressing cells within days of treatment suggest the possibility of an anti-tumour adaptive immune response. In conclusion, NsPEFs not only eliminate N1-S1 HCC tumours, but also may induce an immuno-protective effect that defends animals against recurrences of the same cancer.

Targeted tissue ablation with nanosecond pulses.

In-vivo porcine studies on the effect of nanosecond high voltage pulses on liver tissue have shown that cell death can be induced in well-defined tissue volumes without damaging collagen-predominant structures. Comparison of the experimental results with the results of a three-dimensional finite element model allowed us to determine the threshold electric field for cell death. For 30, 100 nanosecond long pulses this was found to be in the range from 12 to 15 kV/cm. Modelling of the temperature distribution in the tissue using Pennes' bioheat equation showed that the lethal effect of nanosecond pulses on cells is non-thermal. Muscle contractions, generally caused by high voltage pulses, were significantly reduced for the 100 nanosecond pulses compared to microsecond long pulses. The results of these studies indicate that high voltage nanosecond pulses reliably kill normal liver cells in vivo and therefore may be useful for liver tumor treatments.

Electromagnetic energy sources in surgery.

The biophysics, mechanism of actions, applications, benefits and complications of electromagnetic (EM) energy-based surgical instruments, and their current use are reviewed. Understanding the mechanism of action, tissue effects, and appropriate applications of EM devices is critical to achieving an optimal surgical outcome. Although a more diverse range of EM devices are used in human medicine, current use in veterinary medicine is limited to conventional electrosurgery and CO(2) lasers.

Effect of computed tomography display window and image plane on diagnostic certainty for characteristics of dysplastic elbow joints in dogs.

OBJECTIVE: To test the effects of computed tomography (CT) image plane and window settings on diagnostic certainty for CT characteristics associated with dysplastic elbow joints (elbow joint dysplasia) in dogs and to provide optimal display guidelines for these CT characteristics. SAMPLE POPULATION: CT images of 50 dysplastic elbow joints from 49 lame dogs and 10 elbow joints from 5 sound dogs. PROCEDURES: CT image data were obtained in transverse, sagittal, and dorsal planes. Each plane was examined by use of 3 Hounsfield unit (HU) window settings. Two veterinary radiologists independently evaluated sets of CT images for evidence of 7 CT characteristics. Effect of elbow joint status, image plane, and window settings on diagnostic certainty for these CT characteristics was tested by use of a visual analogue scale. RESULTS: Diagnostic certainty for abnormalities of the medial coronoid process (MCP) and radial incisure was highest in the transverse plane, subchondral defects or sclerosis of the trochlea humeri was highest in the dorsal plane, and joint incongruity was highest in the sagittal plane. Certainty for hypoattenuating subchondral defects or fissures was highest at 2,500 or 3,500 HUs, whereas certainty for subchondral sclerosis was highest at 1,500 HUs and lowest at 3,500 HUs. CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic certainty for CT characteristics of elbow joint dysplasia in dogs was affected by image display variables. Diagnostic certainty for altered subchondral bone density was primarily influenced by window settings, whereas structural MCP abnormalities and joint incongruity were influenced most by image plane.

Effect of 9 mm tibial tuberosity advancement on cranial tibial translation in the canine cranial cruciate ligament-deficient stifle.

OBJECTIVE: To assess the effect of 9 mm tibial tuberosity advancement (TTA) on cranial tibial translation (CTT) in a cranial cruciate ligament (CCL)-deficient canine stifle model. STUDY DESIGN: In vitro cadaveric study. ANIMALS: Canine pelvic limbs (n=12). METHODS: Each stifle was placed in a jig at 135 degrees with a simulated quadriceps force and tibial axial force. CTT distance was measured with the CCL intact (iCCL), transected (tCCL), and after performing TTA using a 9 mm cage. RESULTS: Mean CTT for iCCL was 0.42 mm, 1.58 mm after severing the CCL, and 1.06 mm post-TTA. The tCCL CTT measured without any quadriceps force was 2.59 mm. Differences between the intact and tCCL (P<.0001) and tCCL and TTA (P=.0003) were significant. The difference between the tCCL with and without the quadriceps force was not significant (P=.0597). CONCLUSIONS: These data confirm that TTA does reduce CTT in tCCL stifles in this model. The CTT noted was less than that noted clinically. The addition of a simulated quadriceps force to a CCL-deficient stifle before a TTA, by itself, may not significantly lessen CTT. CLINICAL RELEVANCE: Whereas this in vitro model demonstrated that TTA reduced CTT in canine stifles with CCL transected, the model limitations preclude extrapolation to the effect of TTA in a live dog.

Endoscopic-assisted lumbosacral foraminotomy in the dog.

OBJECTIVE: To determine if endoscopic-assisted foraminotomy significantly increased the area of the L7-S1 intervertebral foramen and if, over 12 weeks, stenosis would occur. STUDY DESIGN: Prospective, experimental study. ANIMAL POPULATION: Six clinically normal, 22-29 kg, adult dogs. METHODS: Using endoscopic assistance, unilateral L7-S1 foraminotomy was performed. Computed tomography of L7-S1 was performed preoperatively, immediately postoperatively, and at 12 weeks. Parasagittal foramen area (PFA) measurements were obtained at the entry, middle, and exit zones of the treated and control foramen for each period. Objective and subjective data were compared among dogs by time period and treatment status. RESULTS: Endoscopic-assisted foraminotomy resulted in a significant increase in the mean PFA of the entry and middle zones immediately postoperatively. The exit zone was not significantly larger at any time. The foramen remained significantly larger at 12 weeks only in the middle zone; however, some decrease in the surgically created foramen enlargement occurred at all 3 levels. The procedure was well tolerated but dogs did have transient, mild delay of functional return postoperatively. CONCLUSIONS: Endoscopic-assisted foraminotomy in dogs can be performed for certain foraminal regions, allowing enhanced visibility of the spinal canal. The foramen can be surgically enlarged at the entry and middle zones using this technique; however, some reduction of the foraminal enlargement occurs by 12 weeks. The clinical implications of this reduction cannot be determined from this study. CLINICAL RELEVANCE: Endoscopic-assisted foraminotomy could be used to improve intraoperative visualization in dogs with foraminal stenosis as a component of degenerative lumbosacral stenosis.

One educator's perspective on the role of instructional technology in veterinary surgical education.

A brief overview of the history of instructional technology (IT) use in veterinary surgery education is followed by an assessment of the state of the art in this discipline in the United States. Comments on assessment of teaching tools and the need for a concerted effort at future assessments are made in light of published information regarding the success of alternative learning methods in education in other disciplines. A few final comments are shared about discipline specific technology demands in surgical education and the issue of copyrights versus sharing resources.

Use of computed tomographic densitometry to quantify contrast enhancement of compressive soft tissues in the canine lumbosacral vertebral canal.

OBJECTIVES: To evaluate computed tomography (CT) densitometry as a technique for quantifying contrast enhancement of compressive soft tissues in the canine lumbosacral vertebral canal and to determine whether the degree of contrast enhancement can be used to help predict tissue type or histopathologic characteristics. ANIMALS: 29 large breed dogs with lumbosacral stenosis. PROCEDURE: Contrast-enhanced CT of L5-S3 was performed by use of a previously described protocol. At each disk level, CT densities of a water-filled syringe, epaxial muscles, and 4 vertebral canal locations were measured. Mean tissue enhancement was calculated by vertebral canal location, using water-filled syringe enhancement as a correction factor. Corrected CT enhancement was compared with tissue type, degree of tissue inflammation, and degree of tissue activity. RESULTS: Intravenous contrast administration of contrast medium significantly increased CT densities of water-filled syringes and epaxial muscles. Corrected CT enhancement of vertebral canal soft tissues at stenotic sites was greater than at nonstenotic sites. There was no association between enhancement and tissue type for any vertebral canal location. There was no correlation between enhancement and degree of tissue inflammation. There was a correlation between enhancement and tissue activity in the dorsal vertebral canal only. CONCLUSIONS AND CLINICAL RELEVANCE: A water-filled syringe is a useful calibration tool for CT density measurements. The degree of tissue contrast enhancement, measured by CT densitometry, can be helpful for predicting the location of compressive soft tissues in dogs with lumbosacral stenosis. However, it is of limited value for predicting compressive soft-tissue types or histopathologic characteristics.