BackgroundWe have been developing a non-thermal, drug-free tumor therapy called Nano-Pulse Stimulation (NPS) that delivers ultrashort electric pulses to tumor cells which eliminates the tumor and inhibits secondary tumor growth. We hypothesized that the mechanism for inhibiting secondary tumor growth involves stimulating an adaptive immune response via an immunogenic form of apoptosis, commonly known as immunogenic cell death (ICD). ICD is characterized by the emission of danger-associated molecular patterns (DAMPs) that serve to recruit immune cells to the site of the tumor. Here we present evidence that NPS stimulates both caspase 3/7 activation indicative of apoptosis, as well as the emission of three critical DAMPs: ecto-calreticulin (CRT), ATP and HMGB1.MethodsAfter treating three separate cancer cell lines (MCA205, McA-RH7777, Jurkat E6-1) with NPS, cells were incubated at 37 °C. Cell-culture supernatants were collected after three-hours to measure for activated caspases 3/7 and after 24 h to measure CRT, ATP and HMGB1 levels. We measured the changes in caspase-3 activation with Caspase-Glo® by Promega, ecto-CRT with anti-CRT antibody and flow cytometry, ATP by luciferase light generation and HMGB1 by ELISA.ResultsThe initiation of apoptosis in cultured cells is greatest at 15 kV/cm and requires 50 A/cm2. Reducing this current inhibits cell death. Activated caspase-3 increases 8-fold in Jurkat E6-1 cells and 40% in rat hepatocellular carcinoma and mouse fibrosarcoma cells by 3 h post treatment. This increase is non-linear and peaks at 15–20 J/mL for all field strengths. 10 and 30 kV/cm fields exhibited the lowest response and the 12 and 15 kV/cm fields stimulated the largest amount of caspase activation. We measured the three DAMPs 24 h after treatment. The expression of cell surface CRT increased in an energy-dependent manner in the NPS treated samples. Expression levels reached or exceeded the expression levels in the majority of the anthracycline-treated samples at energies between 25 and 50 J/mL. Similar to the caspase response at 3 h, secreted ATP peaked at 15 J/mL and then rapidly declined at 25 J/mL. HMGB1 release increased as treatment energy increased and reached levels comparable to the anthracycline-treated groups between 10 and 25 J/mL.ConclusionNano-Pulse Stimulation treatment at specific energies was able to trigger the emission of three key DAMPs at levels comparable to Doxorubicin and Mitoxantrone, two known inducers of immunogenic cell death (ICD). Therefore NPS is a physical modality that can trigger immunogenic cell death in tumor cells.
This was a single-site cohort study to evaluate the safety of a new transcervical device (VizAblate™) combining real-time intrauterine sonography with radiofrequency (RF) ablation for the treatment of fibroids. Nineteen women with uterine fibroids received treatment with the VizAblate System in a closed abdomen setting prior to hysterectomy. Twelve of these subjects underwent an immediate abdominal hysterectomy after radiofrequency ablation (acute group), while the remaining seven underwent hysterectomy on post-ablation days 16 and 17 (subacute group). Uteri were sectioned and stained with the viability stain triphenyltetrazolium chloride (TTC) to quantify fibroid ablation dimensions and assess the serosa for thermal injury. Subjects in the subacute group were treated with the VizAblate System under conscious sedation; they provided pain and tolerability data for the interval from ablation through hysterectomy, and indicated overall procedural satisfaction. Twenty-two ablations ranging from 1.8 to 36.2 cm 3 were created among 19 subjects within 20 fibroids and one region of adenomyosis. There were no complications or thermal serosal injury. For subjects in the subacute group receiving one ablation, the mean total procedure time was 25.8±6.0 min (range 18-32 min). All subjects in the subacute group were discharged within 2 h of the VizAblate procedure. For fibroids≤5 cm, 67.2%± 27.0% of the fibroid volume was ablated (range 15-100%; median 75%). Transcervical RF ablation of fibroids under intrauterine sonographic guidance with the VizAblate system can be accomplished with a high degree of reliability and without adverse events.
This paper presents our on-going research at bringing the state-of-the-art in vision and robotics technologies to enhance the emerging minimally invasive surgery, in particular the laparoscopic surgical procedure (Figure 1). A f r amework that utilizes intelligent visual modeling, recognition, and servoing capabilities for assisting the surgeon in maneuvering the scope (camera) in laparoscopy is proposed.The proposed framework integrates top-down model guidance, bottom-up image analysis, and surgeon-in-the-loop monitoring for added patient safety. For the top-down directives, high-level models are used to represent the abdominal anatomy and to encode choreographed scope movement sequences based on the surgeon's knowledge. For the bottom-up analysis, vision algorithms are designed for image analysis, modeling, and matching in a exible, deformable environment (the abdominal cavity). For reconciling the top-down and bottom-up activities, robot servoing mechanisms are realized for executing choreographed scope movements with active vision guidance.The proposed choreographed scope maneuvering concept facilitates the surgeon's control of his/her visual feedback in a handless manner, reduces the risk to the patient from inappropriate scope movements by an assistant, and allows the operation to be p erformed faster and with greater ease. In this paper, we describe the new framework and present some preliminary results on laparoscopic image analysis for segmentation and instrument localization, and on instrument tracking.
This paper describes a practical and reliable image analysis and tracking algorithm to achieve automated instrument localization and scope maneuvering in robotically assisted laparoscopic surgery. Laparoscopy is a minimally invasive surgical procedure that utilizes multiple small incisions on the patient's body through which the surgeon inserts tools and a videoscope in order to conduct an operation. The scope relays images of internal organs to a camera, and the images are displayed on a video screen. The surgeon performs the operation by viewing the scope images rather than performing the traditional “open” procedure, where a large incision is made on the patient's body for direct viewing. The current mode of laparoscopy employs an assistant to hold the scope and position it in response to the surgeon's verbal commands. However, this results in suboptimal visual feedback, because the scope is often aimed incorrectly and vibrates due to hand trembling. We have developed a robotic laparoscope positioner to replace the assistant. The surgeon commands the robotic positioner through a hand/foot controller interface. To further simplify the human‐machine interface that controls the robotic scope positioner, we report here a novel scope‐positioning scheme using automated image analysis and robotic visual servoing. The scheme enables the surgeon to control visual feedback and to perform surgery more efficiently without requiring additional use of the hands. J Image Guid Surg 1:308–325 (1995). © 1996 Wiley‐Liss, Inc.
BACKGROUND Nanosecond pulsed electric field (nsPEF) technology involves delivery of ultrashort pulses of electrical energy and is a nonthermal, drug-free technology that has demonstrated favorable effects on cellular structures of the dermis and epidermis. OBJECTIVE Determine the tolerability and effectiveness of nsPEF treatment of sebaceous gland hyperplasia (SGH). METHODS This study was a prospective, randomized, open-label, multisite, nonsignificant risk trial in which each subject served as their own control. After injection of local anesthetic, high-intensity, ultrashort pulses of electrical energy were used to treat 72 subjects resulting in a total of 222 treated lesions. Subjects returned for 3 to 4 follow-up evaluations with photographs. RESULTS At the final study visit, 99.6% of treated SGH lesions were rated clear or mostly clear and 79.3% of the subjects were satisfied or mostly satisfied with the outcome. At 60 days after nsPEF treatment, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild post-treatment hyperpigmentation. At the last observation for all lesions, 32% of the 222 lesions were noted as having slight volume loss. CONCLUSION Nanosecond pulsed electric field procedure is well tolerated and is very effective in the removal of SGHs. TRIAL REGISTRATION ClinicalTrials.gov NCT03612570.
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