Susan G. Chosy

MONITORING RENAL CRYOSURGERY: PREDICTORS OF TISSUE NECROSIS IN SWINE

PURPOSE To examine parameters for monitoring renal cryosurgery and correlate with histopathologic necrosis in a porcine model. Parameters include: 1) tissue temperature, 2) distance of tissue from the cryosurgical probe insertion site, and 3) inclusion of tissue by the visible iceball. MATERIALS AND METHODS Following midline incision, 6 healthy kidneys from 3 domestic pigs were treated using a nitrogen-based cryosurgical system with 3.4 mm outer diameter cryoprobe. Temperatures were monitored at 6 sites in each kidney using prototype thermocouples. Gross and histologic analysis was performed on tissue harvested from each thermosensor site 24 hours postoperatively. RESULTS All animals survived to complete the full protocol. Post-procedure bleeding was managed surgically. Histopathology revealed that complete ablation was uniformly produced at temperatures of -19.4C or lower in 13/13 tissue samples. Within 16 mm. of the probe insertion site, cells were uniformly ablated in 17/17 samples while degree of tissue death varied widely beyond this margin. Cell death was more likely found at points encompassed by the visible iceball (16/18, 89%) than those beyond it (2/18, 11%) [p <0.0001, Chi-square] while 2/18 (11%) of samples harvested from within the iceball margin were partially viable. CONCLUSIONS Temperature monitoring using thermocouples during porcine renal cryosurgery demonstrated complete homogeneous necrosis of tissues reaching -19.4C or lower. Distance beyond 16 mm. from the cryoprobe and direct visualization of the iceball proved to be less reliable predictors of tissue necrosis. Management of bleeding post-thaw was necessary in every case.

Perivascular and intralesional tissue necrosis after hepatic cryoablation: Results in a porcine model

BACKGROUND Cryosurgical ablation of malignant hepatic tumors is being increasingly used for definitive treatment of metastatic colorectal and primary hepatic tumors. The lack of tumor necrosis near vessels that results from inadequate freezing may contribute to local recurrence and thus limit the applications of this therapy. This study was designed to determine whether single-freeze cryoablation could cause necrosis of both the pervascular and intralesional hepatic parenchyma. METHODS Ten pigs were treated with one 15-minute cycle of cryoablation. Five additional animals were treated with overlapping cryolesions to simulate a double freeze. After 24 hours, animals underwent reoperation with portal vein cannulation and infusion of formalin. Serial sectioning and hematoxylin and eosin staining of cryolesions were performed. RESULTS Complete cell death was visualized within all cryolesions. There was no difference between once or twice-frozen tissue. Vessels within or adjacent to cryolesions showed necrosis of hepatic tissue up to the vessel wall. No sections revealed incomplete necrosis of perivascular hepatic parenchyma. CONCLUSIONS Single-freeze cryoablation results in necrosis of intralesional hepatic parenchyma without added benefit from repeat freezing. Complete necrosis of the perivascular tissue suggests that cryosurgical ablation can effectively cause necrosis immediately adjacent to vessels without concerns of incomplete ablation resulting from the heat sink effect.

Laparoscopic cryosurgery of the kidney in the porcine model: an acute histological study☆

OBJECTIVES To verify histologically whether cryosurgery of the kidney can be accomplished reproducibly without injuring adjacent structures, using a combination of ultrasound and laparoscopic guidance. MATERIALS AND METHODS Six kidneys from three domestic female farm pigs were utilized in the study. Under general anesthesia and after obtaining pneumoperitoneum, the lower pole of the kidney was mobilized laparoscopically and the ureter and adjacent bowel were protected with saline-soaked gauze. Two 3.8 mm-cryoprobes were placed percutaneously into the lower pole and cryoablation was carried out under laparoscopic and ultrasound guidance using a double-freeze technique (10-minute freeze and 5-minute thaw cycles to a probe temperature of -185 degrees C to -196 degrees C) in five kidneys (one control). The kidneys, adjacent ureter and bowel were harvested acutely, and macroscopic, histologic, and electron microscopic evaluation of all specimens was performed. RESULTS Macroscopically, clear margins of cryodestruction corresponded with the ultrasound images of the iceball. In all five treated kidneys, reproducible cell death corresponding to visible margins of cryodestruction were verified histologically. Cell death was further corroborated by electron microscopy. Adjacent structures (ureter and bowel) were sectioned and no significant damage was noted. Blood pressure remained constant throughout the procedure. A crack in the renal parenchyma of one kidney was noted during the thaw phase; at harvest that animal was found to have an intraperitoneal hemorrhage. CONCLUSION Combined laparoscopic and ultrasound-guided cryoablation of the lower pole of the kidney can be accomplished reproducibly in the porcine model without injury to adjacent structures.

Lipid-based blood-pool CT imaging of the liver

RATIONALE AND OBJECTIVES We have recently developed an iodinated lipid-based contrast agent capable of residing in the blood pool for extended periods of time relative to conventional water-soluble contrast agents. The purpose of this study was to examine the effects of combining this new blood-pool agent (ITG-PEG) with a hepatocyte-selective agent (ITG-LE; Molecular Biosystems) for accurate CT detection of small (< 10 mm) VX2 tumors in rabbit liver. MATERIALS AND METHODS Preliminary pharmacokinetic analyses were conducted in SD rats (12) by injection of either I-125-labeled ITG-PEG or I-125-labeled ITG-LE followed by subsequent blood collection and quantification of radioactivity. Preliminary CT studies were conducted in both normal (3) and tumor-bearing NZW rabbits (2). Tumor-bearing rabbits were laparotomized and VX2 cells injected directly into the hepatic parenchyma to produce a total of eight focal lesions (2-10 mm diameter). Animals underwent CT scanning 10 days later with multiple techniques including noncontrast and helical i.v. enhanced (600 mg I/kg iohexol), and then 24 hours later using both ITG-PEG and ITG-LE (200 mg I/kg). Tissue density measurements (HU) of liver, tumor, and blood (descending aorta) were acquired in each case for comparison. Tumor morphology was verified by gross pathologic inspection. RESULTS Pharmacokinetic analysis in rats as well as CT studies in normal rabbits revealed that ITG-PEG remains in the blood-pool phase for more than 2 hours following i.v. administration. In fact, blood density in normal rabbit obtained with ITG-PEG was 95.1 HU +/- 5.8 at 120 minutes compared to 90.7 HU +/- 6.1 immediately after injection. Although liver enhancement was greater with iohexol (67 HU within 1 minute of injection), than for ITG-PEG/ITG-LE (32 HU, 60 minutes postinjection), liver to lesion ratios favored ITG-PEG/ITG-LE due to significant enhancement of tumor itself with iohexol (+40 HU). Tumor enhancement was minimal with ITG-PEG/ITG-LE. Lesions were subjectively much better defined with ITG-PEG/ITG-LE with sharper edge definition. CONCLUSION In these animal models, a new iodinated lipid-based contrast agent composed of both blood pool and hepatocyte-selective components afforded favorable CT imaging results compared to a conventional urographic agent, albeit at one-third the total iodine dose.

Imaging Efficacy of a Hepatocyte-Selective Polyiodinated Triglyceride (DHOG-LE) for Contrast–enhanced CT

RATIONALE AND OBJECTIVES In spite of the widespread use of water-soluble contrast media for computed tomography (CT), an organ-selective contrast agent is still seen as a desirable goal of radiology research (1–3). With its high incidence of primary and metastatic lesions and parenchymal pathology, the liver is one organ system that is likely to benefit from a targeted imaging agent. Although a number of attempts have been made toward developing a safe and effective hepatic CT contrast agent ( 4 –6), a commercially available product resulting from these efforts has yet to become available to clinicians. We have previously introduced and characterized a hepatocyte-selective CT contrast agent consisting of a polyiodinated triglyceride (ITG) in a lipid emulsion (LE) delivery system designed to participate in the naturally occurring lipoprotein metabolism pathways in the liver (7–9). Although this early formulation was effective in providing considerable hepatic opacification for prolonged periods of time after injection, the volumes required for achieving high levels of liver enhancement were potentially limiting. In an effort to reduce the volumes of material required for visualization of hepatic anatomy and pathology by CT, a series of high-concentration ITG-LE formulations was developed (10). The current work extends these improvements and characterizes the imaging efficacy of these high-concentration ITG-LE formulations in normal rats.

Preclinical evaluation of an iodinated particulate contrast agent for use during angiography: work in progress.

PURPOSE To study the feasibility of using an iodinated particulate contrast agent, iodipamide ethyl ester (IDE), for angiography. MATERIALS AND METHODS IDE at doses of 40-100 mg of iodine per kilogram was diluted to a total volume of 5-20 mL and used for digital subtraction angiography in nine dogs under general anesthesia. Equivalent images were obtained by using water-soluble contrast medium (WSCM) for comparison (iohexol) in seven animals. All images were reviewed by blinded reviewers and graded subjectively on a five-point scale. RESULTS Angiographic studies of multiple vascular territories performed with IDE yielded images of slightly lower overall quality compared with images obtained with WSCM (P = .14, Mann-Whitney U test). Arterial phase images were subjectively superior with WSCM when compared with IDE (P < .0001, chi 2.) Depiction of the corresponding veins during the venous phase on the IDE angiograms was superior to that on WSCM angiograms in 12 of 21 cases, although this did not reach statistical significance (P > .05 chi 2). Images of the renal vein and portal vein achieved with IDE were graded as superior to those achieved with WSCM in eight of 10 reviews. CONCLUSION Angiography is feasible with IDE. Compared with WSCM, IDE produced images of lesser quality during the arterial phase, but of equal or superior quality in the venous phase depending on the vessel studied. Because it is excreted slowly in bile and is isotonic, it may prove useful in patients with renal insufficiency, diabetes, multiple myeloma, or severe coronary disease.