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PURPOSE: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101. MATERIAL AND METHODS: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease. RESULTS: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17). CONCLUSION: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection.
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Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Mitomicina/farmacología , Mitomicina/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Estudios Retrospectivos , Ureteroscopía/métodos , Nefronas , Neoplasias Ureterales/tratamiento farmacológico , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Neoplasias Renales/patologíaRESUMEN
Rationale: Focused ultrasound-stimulated microbubbles have been shown to be capable of inducing blood flow shutdown and necrosis in a range of tissue types in an approach termed antivascular ultrasound or nonthermal ablation. In oncology, this approach has demonstrated tumor growth inhibition, and profound synergistic antitumor effects when combined with traditional platforms of chemo-, radiation- and immune-therapies. However, the exposure schemes employed have been broad and underlying mechanisms remain unclear with fundamental questions about exposures, vessel types and sizes involved, and the nature of bubble behaviors and their acoustic emissions resulting in vascular damage - impeding the establishment of standard protocols. Methods: Here, ultrasound transmitters and receivers are integrated into a murine dorsal window chamber tumor model for intravital microscopy studies capable of real-time visual and acoustic monitoring during antivascular ultrasound. Vessel type (normal and tumor-affected), caliber, and viability are assessed under higher pressure conditions (1, 2, and 3 MPa), and cavitation signatures are linked to the biological effects. Results: Vascular events occurred preferentially in tumor-affected vessels with greater incidence in smaller vessels and with more severity as a function of increasing pressure. Vascular blood flow shutdown was found to be due to a combination of focal disruption events and network-related flow changes. Acoustic emissions displayed elevated broadband noise and distinct sub- and ultra-harmonics and their associated third-order peaks with increasing pressure. Conclusions: The observed vascular events taken collectively with identified cavitation signatures provide an improved mechanistic understanding of antivascular ultrasound at the microscale, with implications for establishing a specific treatment protocol and control platform.
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Neoplasias , Animales , Ratones , Humanos , Ultrasonografía , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Acústica , Microvasos/diagnóstico por imagen , Microscopía Intravital , MicroburbujasRESUMEN
Mechanical ultrasound surgery methods use short, high-intensity pulses to fractionate tissues. This study reports the development of a two-step technology for low-energy mechanical ultrasound surgery of tissues using nanodroplets to reduce the pressure threshold. Step 1 consists of vaporizing the nanodroplets into gaseous microbubbles via megahertz ultrasound excitation. Then, low-frequency ultrasound is applied to the microbubbles, which turns them into therapeutic warheads that trigger potent mechanical effects in the surrounding tissue. The use of nanoscale nanodroplets coupled with low-frequency ultrasound reduces the pressure threshold required for mechanical ultrasound surgery by an order of magnitude. In addition, their average diameter of 300 nm can overcome challenges associated with the size of microbubbles. Optimization experiments were performed to determine the ultrasound parameters for nanodroplet vaporization and the subsequent microbubble implosion processes. Optimal vaporization was obtained when transmitting a 2-cycle excitation pulse at a center frequency of 5 MHz and a peak negative pressure of 4.1 MPa (mechanical index = 1.8). Low-frequency insonation of the generated microbubbles at a center frequency of 850, 250 or 80 kHz caused enhanced contrast reduction at a center frequency of 80 kHz, compared with the other frequencies, while operating at the same mechanical index of 0.9. Nanodroplet-mediated insonation of ex vivo chicken liver samples generated mechanical damage. Low-frequency treatment at a mechanical index of 0.9 and a center frequency of 80 kHz induced the largest lesion area (average of 0.59 mm2) compared with 250- and 850-kHz treatments with the same mechanical index (average lesions areas of 0.29 and 0.19 mm2, respectively, p < 0.001). The two-step approach makes it possible to conduct both the vaporization and implosion stages at mechanical indices below 1.9, thus avoiding undesired mechanical damage. The findings indicate that coupled with low-frequency ultrasound, nanodroplets can be used for low-energy mechanical ultrasound surgery.
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Microburbujas , Ultrasonografía , VolatilizaciónRESUMEN
OBJECTIVE: Current minimally invasive techniques for ablation in superficial venous reflux are limited to thermal based systems requiring tumescent anesthesia, non-thermal chemical sclerosants and permanent glue implantation. The aim of this feasibility study was to determine the safety and efficacy of a novel mechanical-only ablation (MOA) device called EnVena, in a recognised large animal model with chronic follow up. METHODS: Venous ablation of six lateral saphenous veins in three sheep was performed using the EnVena device. Luminal patency and vein wall fibrosis were evaluated by histologic analysis at 51 and 89 days. RESULTS: All treated veins demonstrated fibrotic occlusion in contiguous segments at 51 and 89 days on histological analysis. From 45 consecutive segments spanning the treatment length across the six treated veins, 26 (57%) were fully occluded, 7 (16%) were impinged or partially occluded and 12 (27%) were open. There were no device related complications during the follow up period. CONCLUSIONS: A purely mechanical approach to superficial venous ablation demonstrated safety and efficacy in a recognized large animal model based on histological findings.
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Ablación por Catéter , Várices , Insuficiencia Venosa , Animales , Vena Safena/patología , Vena Safena/cirugía , Soluciones Esclerosantes , Escleroterapia , Ovinos , Resultado del Tratamiento , Várices/terapia , Insuficiencia Venosa/patología , Insuficiencia Venosa/cirugíaRESUMEN
INTRODUCTION: There are currently not many publications on the safety of thermomechanical ablation (TMA) devices, and those that are published only have small numbers of subjects. This treatment is gaining popularity in Europe and Asia, and thus there is a need to look at the safety of this treatment. OBJECTIVE: The purpose of this retrospective study was to evaluate the safety of the clinical use of the novel TMA system (Tixel, Novoxel, Israel) for facial rejuvenation and treatment of acne scars. METHODS: We did a retrospective review of our first 150 patients who were treated with the TMA device. RESULTS: One hundred and fifty consecutive patients aged 20 years to 82 years with Fitzpatrick skin types I to V treated with the TMA device were included in this study. The total number of treatment sessions was 327 (average 2.18 treatment per patient). The total number of pulses delivered to these patients was 1 48 856 (average 455 pulses per session). The indications for the treatment were photodamaged skin (n=145) and acne scarring (n=5). All patients were able to use makeup immediately after the treatment at lower settings, thus needing no real recovery time. Patients treated at higher settings were able to use makeup after 2 days. There were four reported complications: post-inflammatory hyperpigmentation (n=2), impetigo (n=1), and dermatitis (n=1). CONCLUSIONS: Using the TMA device in the treatment of photodamage and acne scarring is safe in skin types I to V and has a low incidence of temporary side effects with no permanent side effects.
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Acné Vulgar , Envejecimiento de la Piel , Acné Vulgar/complicaciones , Acné Vulgar/terapia , Adulto , Cicatriz/etiología , Cicatriz/patología , Cicatriz/terapia , Humanos , Rejuvenecimiento , Estudios Retrospectivos , Piel/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
Previous chapters introduced the ability of using focused ultrasound to ablate tissues. It has led to various clinical applications in the treatment of uterine fibroid, prostate or liver cancers. Nevertheless, treating the brain non-invasively with focused ultrasound has been considered beyond reach for almost a century: The skull bone protects the brain from mechanical injuries, but it also reflects and refracts ultrasound, making it difficult to target the brain with focused ultrasound. Fortunately, aberration correction techniques have been developed recently and thermal lesioning in the thalamus has been achieved clinically. This chapter introduces the aberration effect of the skull bone and how it can be corrected non-invasively. It also presents the latest clinical results obtained with thermal ablation and introduces novel non-thermal approaches that could revolutionize brain therapy in the future.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Imagen por Resonancia Magnética Intervencional/métodos , Cráneo/patología , Tálamo/cirugía , HumanosRESUMEN
Both mechanical ablation and laser ablation have been introduced for removal of the corneal epithelium in excimer laser photorefractive keratectomy(PRK). We analyzed the differences of the clinical outcome between mechanical ablation and laser ablation on 256 consecutive eyes followed up more than 6 months after PRK from August 1991 to June 1993. During the follow up period. pre- and post- operative visual acuity, refractive errors, corneal clarity, epithelial healing time, post-operative pain, and central island were compared between two groups. Anova and X2 test were used for statistical analysis. The uncorrected visual acuity at 6 months after operation was 0.81 in group A and 0.75 in group B(p<.05). The degree of corneal haziness was more severe in group B than group A at 6 months after operation(p<.05). Mean refractive errors and keratometer readings were not statistically signigicant between two groups. Average epithelial healing times after operation were 3.18 days in group A and 2.73 days in group B(p<.001). The incidence ot central island was lower in group B than in group A(p<.001). Post-operative pain was less severe in group B than in group A. This results suggest that mechanical ablation seems to achieved better visual acuity and less complication than laser ablation for removal of the corneal epithelium in PRK.