Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience

PURPOSE

We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors.

METHODS

We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment-related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated.

RESULTS

No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis.

CONCLUSION

The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation.About 70% of hepatic metastases are nonresectable because of their anatomic location, the presence of comorbidities, or limited hepatic functional reserve (1). In these patients and in case of nonresectable primary liver tumors, percutaneous thermal ablation procedures, such as radiofrequency (RF) and microwave ablation, have become effective tools for treating hepatic malignancies (2–4). However, the effectiveness of RF and microwave treatment may be limited, either because of thermal damage to temperature-sensitive structures located in close proximity to the target tissue (5) or because of incomplete ablation of tumors adjacent to major hepatic vessels due to a phenomenon commonly termed “heat-sink effect” (6–10) which describes the loss of the applied thermal energy through the blood flow in those major vessels, whereby the effective energy application remains inadequate to ablate the target lesion.Irreversible electroporation (IRE) is a theoretically nonthermal ablation technique that delivers a series of high-voltage millisecond electrical pulses to the surrounding tissue, thus leading to irreversible disruption of the integrity of cell membranes and subsequent cell death by apoptosis (11–14). IRE may overcome the problems raised with thermal ablation: previous animal studies reported that bile ducts, blood vessels, nerves, and connective tissues are affected by IRE; however, regeneration is possible to some extent due to preservation of the tissue architecture (12, 13, 15–19). Moreover the feasibility of inducing cell death up to a vessel wall without any perivascular sparing was shown with IRE (12, 13, 18). The safety of IRE in the treatment of humans has been described (20). First reports have described potential complications after IRE, such as hemorrhage requiring blood transfusion (1.2%, two of 167 ablation procedures), portal vein thrombosis (3.2%, one of 31 ablation procedures), injury to bile ducts (1.8%, three of 167 ablation procedures), and infection (3.6%, six of 167 ablation procedures) (21, 22). However, few data are available for evaluating the potential risk factors associated with the occurrence of post-IRE complications.The purpose of this study was to review the frequency of mortality and morbidity after computed tomography (CT) fluoroscopy-guided liver IRE conducted at a single center and assess the factors influencing the occurrence of major complications.     

Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase.

Overlapping cloned cDNAs representing the entire sequence of the rat fatty acid synthase mRNA have been isolated from a cDNA library and sequenced. Authenticity of the cDNA clones was supported by hybridization to fatty acid synthase mRNA and by amino-terminal sequencing of 39 fatty acid synthase CNBr fragments. The full-length fatty acid synthase mRNA is 9156 nucleotides long and includes an 84-nucleotide 5' noncoding region, a 7515-nucleotide coding sequence, and a 1537-nucleotide 3' noncoding region; a second mRNA species containing a shortened 3' noncoding sequence is also transcribed in the rat. The encoded fatty acid synthase subunit contains 2505 amino acids and has a molecular weight of 272,340. Active sites and substrate binding sites were located within the sequence, thus establishing the order of domains on the multifunctional animal fatty acid synthase as condensing enzyme-transferase-dehydrase-enoyl reductase-ketoreductase-acyl carrier protein-thioesterase.     

Alloimmunization to platelets in heavily transfused patients with sickle cell disease

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.