Recent comprehensive investigations clarified that immune microenvironment surrounding tumor cells are deeplyinvolved in tumor progression, metastasis, and response to treatment. Furthermore, several immunotherapeutic trialshave achieved successful results, and the immunotherapeutic agents are available in clinical practice. To enhancetheir demonstrated efficacy, combination of immunotherapy and ablation has begun to emerge. Local ablationshave considerable advantages as an alternative therapeutic option, especially its minimal invasiveness. In addition,local ablations have shown immune-regulatory effect in preclinical and clinical studies. Although the correspondingmechanisms are still unclear, the local ablations combined with immunotherapy have been suggested in the treatmentof several solid malignancies. This article aims to review the published data on the immune-regulatory effectsof local ablations including stereotactic body radiotherapy, cryoablation, radiofrequency ablation, and high-intensityfocusedultrasound. We also discuss the value of local ablations combined with immunotherapy. Local ablations havethe potential to improve future patient outcomes; however, the effectiveness and safety of local ablations combinedwith immunotherapy should be further investigated.

STUDY DESIGN: Experimental human study. PURPOSE: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. OVERVIEW OF LITERATURE: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. METHODS: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription–polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. RESULTS: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. CONCLUSIONS: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.
Chemokine CCL2 ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-6 ; Spinal Stenosis ; Stress, Mechanical ; Synovial Membrane ; Synovitis ; Zygapophyseal Joint

A 72-year-old woman was scheduled to undergo aortic valve replacement for aortic stenosis when she was diagnosed with heparin-induced thrombocytopenia type II after a decrease in platelets was detected. Although postponement was considered, the operation went ahead as scheduled because of unstable hemodynamics. Continuous intravenous infusion of argatroban (4 mg/kg/min) was initiated at the start of the operation, and nafamostat mesylate (30 mg/h) was initiated when cardiopulmonary bypass was started. Activated coagulation time was monitored, and the dose of argatroban was adjusted accordingly. Argatroban administration was terminated after removal of aortic cross-clamping, and cardiopulmonary bypass was stopped 1 h later. The operation was completed 7 h after stopping cardiopulmonary bypass due to difficulties in hemostasis. Operation time was 12 h 21 min, cardiopulmonary bypass time was 3 h 10 min, blood loss was 3444 mL, and blood transfusion volume was 6400 mL. The amount of argatroban administered was lower in our case than in previously reported cases, but blood loss after stopping cardiopulmonary bypass could not be reduced in our case.

Patent ductus arteriosus (PDA) is a rare congenital cardiovascular anomaly in cats. Due to their small body, intercostal thoracotomy is the most common option to close the PDA.However, few reports detail the surgical technique for ligating PDA in kittens. In this case report, three cats weighing 1.4 kg, 1.2 kg, and 2.9 kg were diagnosed PDA. Clip ligation via left fourth intercostal thoracotomy was performed and the cats were successfully treated.Postoperative echocardiography showed no residual flow in any of the cases. This case report highlights clip occlusion for small cats with PDA could be safe and effective.