Irreversible electroporation in eradication of rabbit VX2 liver tumor.

PURPOSE: To show the effectiveness and safety of irreversible electroporation (IRE) in treating large tumor models. MATERIALS AND METHODS: VX2 liver tumor implantation was performed in 35 New Zealand White Rabbits. The rabbits were divided into three groups 1 week after implantation. The control group included 15 rabbits; the remaining 20 rabbits were divided into two IRE treatment groups. For the treatment groups, 10 rabbits underwent ablation with a single IRE application (IRE-S group), and 10 rabbits underwent ablation with multiple IRE applications (IRE-M group). Treatments and outcomes were analyzed using ultrasound, contrast-enhanced computed tomography (CT), and immunohistologic staining (hematoxylin and eosin [H&E], P-53, Ki-67, CD30, and vascular endothelial growth factor receptor [VEGFR] staining, and terminal deoxynucleotidyl-transferase-mediated 2'-deoxyuridine 5'-triphosphate [dUTP]-biotin nick-end labeling [TUNEL] assay). RESULTS: Multiple IRE ablations consistently produced complete cell death in all the animals in the IRE-M group (n = 10, IRE ablation time 2.45 minutes ± 0.3). The results were validated with ultrasound, CT, H&E, Ki-67, P53, and TUNEL assay. A high level of CD30-positive cells were identified in the IRE groups. A sharply demarcated ablation zone with no damage to surrounding vital structures was observed in all IRE-treated tissues. No complications during or after ablation were observed in any of the animals. CONCLUSIONS: The effects of IRE were shown in a large tumor model with single and multiple IRE ablations (IRE-S and IRE-M treatment groups); complete ablation of the tumor was seen in the IRE-M group. These findings successfully show the beneficial effects and safety of IRE in the treatment of tumors and validate its potential as a clinically translatable treatment.

Safety of Irreversible Electroporation Ablation of the Pancreas.

OBJECTIVES: To evaluate the safety of irreversible electroporation (IRE) on swine pancreatic tissue including its effects on peripancreatic vessels, bile ducts, and bowel. METHODS: Eighteen Yorkshire pigs underwent IRE ablation of the pancreas successfully and without clinical complications. Contrast-enhanced computed tomography angiography and laboratory studies before the IRE ablation with follow-up computed tomography angiography, laboratory testing, and pathological examination up to 4 weeks postablation were performed. RESULTS: In a subset of cases, anatomic peripancreatic vessel narrowing was seen by 1 week postablation, persisting at 4 weeks postablation, without apparent functional impairment of blood flow. Laboratory studies revealed elevated amylase and lipase at 24 hours post-IRE, suggestive of acute pancreatitis, which normalized by 4 weeks post-IRE. There was extensive pancreatic tissue damage 24 hours after IRE with infiltration of immune cells, which was gradually replaced by fibrotic tissue. Ductal regeneration without loss of pancreatic acinar tissue and glandular function was observed at 1 and 4 weeks postablation. CONCLUSIONS: In our study, we demonstrated and confirmed the safety and minimal complications of IRE ablation in the pancreas and its surrounding vital structures. These results show the potential of IRE as an alternative treatment modality in patients with pancreatic cancer, especially those with locally advanced disease.

Dosimetry of Y-90 Microspheres Utilizing Tc-99m SPECT and Y-90 PET.

Dosimetry for yttrium-90 radioembolization continues to generate interest and controversy, as multiple approaches have been used effectively. Traditionally, simple formulas primarily based on patients' body weight or perfused liver volume were used. Over the past several years, dosimetry refinements have led to marked improvements in this therapy from both a safety and efficacy standpoint. Technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) optimizes pretreatment dosimetry to ensure delivery of a therapeutic radiation dose to the tumor while minimizing nontarget radiation to healthy hepatic tissue. Post-treatment yttrium-90 PET utilizing the inherent internal pair production of yttrium-90 accurately calculates the absorbed dose to tumors and to the normal hepatic parenchyma, which correlates with patient outcomes. As dosimetric calculations become more complex, quantitative imaging with Tc-99m SPECT and Y-90 PET may set the new standard for radioembolization dosimetry.

Y90 selective internal radiation therapy.

Primary liver malignancies and liver metastases are affecting millions of individuals worldwide. Because of their late and advanced stage presentation, only 10% of patients can receive curative surgical treatment, including transplant or resection. Alternative treatments, such as systemic chemotherapy, ablative therapy, and chemoembolization, have been used with marginal survival benefits. Selective internal radiation therapy (SIRT), also known as radioembolization, is a compelling alternative treatment option for primary and metastatic liver malignancies with a growing body of evidence. In this article, an introduction to SIRT including background, techniques, clinical outcomes, and complications is reviewed.

Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Portal Hypertensive Variceal Bleeding: Preliminary Results.

OBJECTIVES: To describe the technical feasibility, safety, and clinical outcomes of coil-assisted retrograde transvenous obliteration (CARTO) in treating portal hypertensive non-esophageal variceal hemorrhage. METHODS: From October 2012 to December 2013, 20 patients who received CARTO for the treatment of portal hypertensive non-esophageal variceal bleeding were retrospectively evaluated. All 20 patients had at least 6-month follow-up. All patients had detachable coils placed to occlude the efferent shunt and retrograde gelfoam embolization to achieve complete thrombosis/obliteration of varices. Technical success, clinical success, rebleeding, and complications were evaluated at follow-up. RESULTS: A 100% technical success rate (defined as achieving complete occlusion of efferent shunt with complete thrombosis/obliteration of bleeding varices and/or stopping variceal bleeding) was demonstrated in all 20 patients. Clinical success rate (defined as no variceal rebleeding) was 100%. Follow-up computed tomography after CARTO demonstrated decrease in size with complete thrombosis and disappearance of the varices in all 20 patients. Thirteen out of the 20 had endoscopic confirmation of resolution of varices. Minor post-CARTO complications, including worsening of esophageal varices (not bleeding) and worsening of ascites/hydrothorax, were noted in 5 patients (25%). One patient passed away at 24 days after the CARTO due to systemic and portal venous thrombosis and multi-organ failure. Otherwise, no major complication was noted. No variceal rebleeding was noted in all 20 patients during mean follow-up of 384±154 days. CONCLUSIONS: CARTO appears to be a technically feasible and safe alternative to traditional balloon-occluded retrograde transvenous obliteration or transjugular intrahepatic portosystemic shunt, with excellent clinical outcomes in treating portal hypertensive non-esophageal variceal bleeding.

Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.

Pituitary adenomas can appear as hypermetabolic lesions in (18) F-FDG PET imaging.

OBJECTIVE: The 2-deoxy-2-[(18) F] fluoro-D-glucose positron emission tomography (FDG-PET) scan is commonly used in detection and staging of many malignant neoplasms. However, several benign or non-neoplastic conditions avidly accumulate (18) F-FDG, causing ambiguity in interpretation of results. It is unknown whether pituitary adenomas uptake (18) F-FDG and appear positive in PET imaging. Here, we present 2 cases of benign pituitary adenoma with elevated metabolic activity in (18) F-FDG PET scan. METHODS: Medical, neurologic, and psychiatric histories; physical examination findings; laboratory work up results; and pathologic and imaging studies were documented. RESULTS: The (18) F-FDG-PET images revealed foci of marked FDG uptake in pituitary adenomas of 2 patients. CONCLUSION: Pituitary micro- and macro-adenomas may present as hypermetabolic foci on (18) F-FDG PET scan.

Dual regulation of the cardiac L-type calcium channel in L6 cells by protein kinase C.

The role of protein kinase C (PKC) in the regulation of cardiac L-type Ca(2+) channel activity (LCC) was investigated in L6 rat neonatal myoblasts. Depolarization of fura-2 loaded cells with 140mM KCl activated a Ba(2+) influx pathway that was blocked by nifedipine and stimulated by (-) Bay K 8644. At least two splice variants of the alpha(1C) subunit of the cardiac LCC were identified by PCR; the alpha(1S) subunit of the skeletal muscle LCC was not detected. Peptides that specifically inhibit translocation of the novel, Ca(2+)-independent delta and epsilon PKC isozymes reduced Ba(2+) influx by 27% and 19%, respectively, whereas a corresponding peptide directed against translocation of classical PKC alpha had no effect. Ingenol 3,20-dibenzoate, an agent reported to selectively activate novel PKCs, increased Ba(2+) uptake by 31% while ethanol, a PKC epsilon agonist, enhanced uptake by 38%. In contrast, selective activation of classical PKCs with thymeleatoxin or an agonist peptide reduced Ba(2+) influx by 23-33%. Ba(2+) influx was reduced by 30-40% when cells were treated with either a PKC inhibitor (Gö 6983, bisindolylmaleimide) or the PKC activator phorbol-12-myristate-13-acetate. We propose that novel, Ca(2+)-insensitive PKC(s) enhance cardiac Ca(2+) channel activity in L6 cells under basal conditions while activation of the classical, Ca(2+)-sensitive PKC(s) inhibits channel activity. These findings provide the first evidence that different PKC isozymes exert class-specific opposing effects on cardiac L-type Ca(2+) channel activity in L6 myoblasts.

Influence of meniscectomy and meniscus replacement on the stress distribution in human knee joint.

Studying the mechanics of the knee joint has direct implications in understanding the state of human health and disease and can aid in treatment of injuries. In this work, we developed an axisymmetric model of the human knee joint using finite element method, which consisted of separate parts representing tibia, meniscus and femoral, and tibial articular cartilages. The articular cartilages were modeled as three separate layers with different material characteristics: top superficial layer, middle layer, and calcified layer. The biphasic characteristic of both meniscus and cartilage layers were included in the computational model. The developed model was employed to investigate several aspects of mechanical response of the knee joint under external loading associated with the standing posture. Specifically, we studied the role of the material characteristic of the articular cartilage and meniscus on the distribution of the shear stresses in the healthy knee joint and the knee joint after meniscectomy. We further employed the proposed computational model to study the mechanics of the knee joint with an artificial meniscus. Our calculations suggested an optimal elastic modulus of about 110 MPa for the artificial meniscus which was modeled as a linear isotropic material. The suggested optimum stiffness of the artificial meniscus corresponds to the stiffness of the physiological meniscus in the circumferential direction.