Chang Yell Lee

New Surgical Instruction Method for Homium Laser Enucleation of the Prostate, “Hand-Grab Navigated Technique,” to Shorten the Learning Curve: The Results of Multicenter Analysis

To introduce a new surgical mentorship, the “hand‐grab navigated technique,” to shorten the learning curve for Holmium laser enucleation of the prostate.

MP73-14 CAPABILITY OF ELECTRICAL IMPEDANCE SPECTROSCOPY SENSOR ON A NEEDLE AS A NOVEL TOOL TO ESTIMATE MALIGNANT RENAL TUMOR MARGIN: EX-VIVO DEMARCATION OF TUMOR AND SURGICAL MARGIN

INTRODUCTION AND OBJECTIVES: The combination of the human immunodeficiency virus (HIV) protease inhibitors lopinavir and ritonavir has been a standard regimen used to treat HIV infection. Ritonavir acts as a chemical booster to enhance lopinavir’s activity. Lopinavir has recently been shown to act against cancer by inducing endoplasmic reticulum (ER) stress, and we thought that the combination would kill renal cancer cells by inducing robust ER stress. METHODS: The viability and clonogenicity of renal cancer cells (769-P, 786-O, Caki-2) treated with clinically feasible concentrations of lopinavir (10-40 mM) and/or ritonavir (5-10 mM) were assessed by MTS assay and colony formation assay. Apoptosis was evaluated by annexin-V assay. Cell cycle analysis was done using flow cytometry. Induction of ER stress and the expression of cell-cycle regulators, apoptosis-associated proteins, NOXA, Akt, BCL-2, and survivin were evaluated by western blot analysis. Drug synergism was assessed by the Chou-Talalay method. RESULTS: Lopinavir in combination with ritonavir inhibited renal cancer growth synergistically (combination index <1). The combination also inhibited clonogenic survival of cancer cells significantly (p <0.05). It perturbed the cell cycle by inhibiting the expression of cyclin D1 and cyclin-dependent kinase 4, increasing the cells in the sub-G1 fraction. The combination caused apoptosis synergistically: 10-20 mM lopinavir increased the number of annexin-V positive cells and the expression of cleaved poly(ADP-ribose) polymerase slightly but in combination with 10 mM ritonavir increased both drastically. As expected, the combination induced ER stress evidenced by the increased expression of the ER stress markers glucose-regulated protein 78 and endoplasmic reticulum resident protein 44. Furthermore, increased expression of NOXA confirmed that the combination-induced apoptosis was a result of ER stress. We also found that the combination decreased the expression of the antiapoptotic proteins BCL-2 and survivin by inhibiting the Akt signaling pathway. CONCLUSIONS: The combination of lopinavir and ritonavir induces ER stress and causes renal cancer apoptosis synergistically. Inhibition of the Akt pathway is another important mechanism of its action.

MP92-20 DIFFERENTIATION BETWEEN NORMAL AND CANCEROUS RENAL TISSUES USING ELECTRICAL IMPEDANCE SPECTROSCOPY NEEDLE.

INTRODUCTION AND OBJECTIVES: Orthotopic xenografts are increasingly used preclinical in-vivo models for the study of renal cell carcinoma (RCC). However, monitoring of these tumors requires sophisticated imaging techniques. Herein we comparatively evaluated modern small animal imaging tools like high-resolution 3D-ultrasonography (3D-US), contrast-enhanced in-vivo micro-CT (CE-CT) and 9,4T MRI (MRI) to monitor tumor growth in an orthotopic RCC xenograft model. METHODS: 10 CAKI-1 cells were injected under the renal capsule of 18 Balb/c-nude mice. Every 14 days from week 4 imaging was performed by CE-CT and 3D-US. 10 weeks after cell inoculation, all animals additionally underwent MRI. At autopsy, tumor volumes were determined with a caliper and compared to in-vivo imaging results. CE-CT, MRI and 3D-US were evaluated regarding tumor detection, tumor volume analysis, radiographic imaging properties and examination time. Finally, RCC cell lines KTCTL30 (n1⁄42) and 786-0 (n1⁄41) were used to test their applicability for the orthotopic xenograft model. RESULTS: In 16/18 animals (take rate 89%) all methods enabled to adequately visualize orthotopic tumors and to display their growth over time. While the tumors had a homogenously radiolucent signal in CE-CT, 3D-US and MRI could better visualize intratumoral structures and surrounding soft tissue. CT had the best spatial resolution, followed by 3D-US and MRI. Median examination time was 4.8min per 3D-US, 12.5min per CT and 37.9min per MRI, respectively. Of interest, tumor volumes determined by CE-CT and 3D-US showed strong correlation with each other (n1⁄485, R1⁄40.985) as well as with caliper measurements at autopsy (CT: n1⁄416. R1⁄40.922; 3D-US: n1⁄416, R1⁄40.934). Similarly, tumor volumes measured with T2w MRI correlated well with those determined by CT, 3D-US and caliper. No side effects due to radiation exposure were seen. Mice inoculated with KTCTL30 cells developed partly cystic, partly solid tumors. 786-O cells yielded purely solid, fast growing tumors. CONCLUSIONS: All three imaging modalities are feasible tools for a non-invasive monitoring of orthotopic tumor growth and show excellent correlation with each other. While 3D-US allows for a fast analysis of tumor volume with excellent resolution, MRI provides the best soft tissue contrast and can give additional information about tumor biology (e.g. diffusion, perfusion). CT has the best spatial resolution and enables simultaneous screening for bone and lung metastases but relies on the use of contrast agent and ionizing radiation.