Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model.

The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1 MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n = 8) and wild-type (n = 8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and subendothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasoundexposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery.

The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) emphasizes the importance of optimizing treatment for the disease. Historical protocol has utilized definitive radiation and invasive open procedures; these techniques expose the patient to significant risks and morbidity. Transoral robotic surgery (TORS) has emerged as a therapeutic modality with promise. Here, the literature regarding proper patient selection and other considerations for this procedure was reviewed. Multiple patient and tumor-related factors were found to be relevant for successful use of this treatment strategy. Outcomes regarding early and advanced-stage OPSCC were analyzed. Finally, the literature regarding use of TORS in three distinct patient populations, individuals with primary OPSCC, carcinoma of unknown primary and those with recurrent OPSCC, was examined.

Objective: Chemoradiotherapy (cRT) and total laryngectomy (TL) are acceptable treatments for locally advanced laryngeal squamous cell carcinoma (LSSC). We aimed to compare the outcomes in patients receiving full-dose treatment. Methods: We identified 11,237 patients in the National Cancer Database treated 2004 to 2015 for T3-4N0-3 LSCC with either TL (with 60 to 80 Gy of adjuvant RT) or cRT (70 to 80 Gy). We evaluated differences in overall survival (OS) using Kaplan-Meier and Cox proportional hazards modeling. Results: For patients with T3 disease, there was no difference in OS regardless of N stage (N0: hazard ratio [HR]=0.94, P=0.38; N+: HR=0.92, P=0.19). TL was associated with improved OS in patients with T4 disease (N0: HR=1.39, P<0.001; N+: HR=1.22, P=0.001). Conclusion: In patients who receive optimal therapy, both TL and cRT offer similar outcomes in T3 but not T4a disease.

Background and Purpose-Ultrasound has been shown to increase recombinant tissue plasminogen activator thrombolysis through stable cavitation, or sustained bubble activity, but this mechanism needs further optimization. Use of low-frequency ultrasound in combination with microbubbles stabilized against dissolution, in the form of ultrasound contrast agents, has resulted in greater lytic efficacy in vitro. Summary of Review-This article reviews the motivation for developing ultrasound-enhanced thrombolysis and the existing evidence for its potential as an intervention for ischemic stroke. Stable cavitation is discussed and current in vitro and ex vivo studies of bubble-mediated recombinant tissue plasminogen activator clot lysis are summarized. Conclusions-Ultrasound-driven stable cavitation nucleated by an infusion of an echo contrast agent facilitates recombinant tissue plasminogen activator thrombolysis. Optimization of this gently effervescent phenomenon has the potential to reduce the morbidity and mortality of victims of ischemic stroke.