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Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections, and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical wash-out when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity, for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

Large intra-abdominal, retroperitoneal and intramuscular hematomas are common consequences of sharp and blunt trauma and post-surgical bleeds, and often threaten organ failure, compartment syndrome or spontaneous infection. Current therapy options include surgical evacuation and placement of indwelling drains that are not effective because of the viscosity of the organized hematoma. We have previously reported the feasibility of using boiling histotripsy (BH)—a pulsed high-intensity focused ultrasound method—for liquefaction of large volumes of freshly coagulated blood and subsequent fine-needle aspiration. The goal of this work was to evaluate the changes in stiffness of large coagulated blood volumes with aging and retraction in vitro, and to correlate these changes with the size of the BH void and, therefore, the susceptibility of the material to BH liquefaction. Large-volume (55–200 mL) whole-blood clots were fabricated in plastic molds from human and bovine blood, either by natural clotting or by recalcification of anticoagulated blood, with or without addition of thrombin. Retraction of the clots was achieved by incubation for 3 h, 3 d or 8 d. The shear modulus of the samples was measured with a custom-built indentometer and shear wave elasticity (SWE) imaging. Sizes of single liquefied lesions produced with a 1.5-MHz high-intensity focused ultrasound transducer within a 30-s standard BH exposure served as the metric for susceptibility of clot material to this treatment. Neither the shear moduli of naturally clotted human samples (0.52 ± 0.08 kPa), nor their degree of retraction (ratio of expelled fluid to original volume 50%–58%) depended on the length of incubation within 0–8 d, and were significantly lower than those of bovine samples (2.85 ± 0.17 kPa, retraction 5%–38%). In clots made from anticoagulated bovine blood, the variation of calcium chloride concentration within 5–40 mmol/L did not change the stiffness, whereas lower concentrations and the addition of thrombin resulted in significantly softer clots, similar to naturally clotted human samples. Within the achievable shear modulus range (0.4–1.6 kPa), the width of the BH-liquefied lesion was more affected by the changes in stiffness than the length of the lesion. In all cases, however, the lesions were larger compared with any soft tissue liquefied with the same BH parameters, indicating higher susceptibility of hematomas to BH damage. These results suggest that clotted bovine blood with added thrombin is an acceptable in vitro model of both acute and chronic human hematomas for assessing the efficiency of BH liquefaction strategies.

Protein-losing enteropathy manifests as a loss of serum proteins through the gastrointestinal tract, resulting in hypoproteinemia, extravascular fluid retention, and edema. Management consists of nutritional maintenance in conjunction with interventions targeted at treating the underlying etiology. This report describes a patient with protein-losing enteropathy from a central conducting lymphatic obstruction who was treated with percutaneous extra-anatomic lymphovenous bypass creation. A modified gun-sight technique was used to create a lymphovenous bypass between an occluded terminal thoracic duct and the left internal jugular vein. A percutaneous technique to reconstruct the terminal thoracic duct via lymphovenous bypass creation was feasible.

Abscesses are walled-off collections of infected fluids that often develop as complications in the setting of surgery and trauma. Treatment is usually limited to percutaneous catheterization with a course of antibiotics. As an alternative to current treatment strategies, a histotripsy approach was developed and tested in a novel porcine animal model. The goal of this article is to use advanced ultrasound imaging modes to extract sonographic features associated with the progression of abscess development in a porcine model. Intramuscular or subcutaneous injections of a bi-microbial bacteria mixture plus dextran particles as an irritant led to identifiable abscesses over a 2 to 3 wk period. Selected abscesses were imaged at least weekly with B-mode, 3-D B-mode, shear-wave elastography and plane-wave Doppler imaging. Mature abscesses were characterized by a well-defined core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. 3-D imaging demonstrated the natural history of abscess morphology, with the abscess becoming less complex in shape and increasing in volume. Furthermore, shear-wave elastography demonstrated variations in stiffness as phlegmon becomes abscess and then liquefies, over time. These ultrasound features potentially provide biomarkers to aid in selection of treatment strategies for abscesses.

Abscesses are walled-off collections of infected fluids that often develop as complications in the setting of surgery and trauma. Abscess care depends on size, location, composition and complexity, among other patient factors. The goal of this work is to describe, using the latest ultrasound imaging technologies, the progression of abscess development in a porcine animal model. Intramuscular or subcutaneous injections of bacteria plus dextran particles as an irritant led to identifiable abscesses over a 2- to 3-week period. The abscesses were imaged at least weekly with B-mode, 3D B-mode, shear-wave elastography (SWE) and color flow imaging. Mature abscesses were characterized by a well-defined core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. Size and shape changes during development were quantified with 3D imaging. With SWE, the lesion stiffness varied interiorly and generally decreased over time. These ultrasound features potentially provide biomarkers to facilitate improved selection of treatment strategies for abscesses.

Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections, and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical wash-out when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity, for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

Abscesses are walled-off collections of infected fluids most often treated with percutaneous drains placed under CT guidance. Complications such as clogged drains or secondary infections require rehospitalization and wound management. Histotripsy treatment has the potential to eliminate the need for long term catheterization and antibiotics. The progression of abscess development has yet to be fully described. The objective of this study was to use the latest advances in non-contrast ultrasound technologies to characterize abscess development in a porcine animal model. Intramuscular or subcutaneous injections of bacteria plus dextran particles as an irritant led to identifiable abscesses over a 2- to 3-week period. Ultrasound imaging was performed at least weekly, in some cases with a 3D tracking device that provided quantifiable size and shape measurements. Abscess progression was also measured with a plane-wave Doppler mode providing increased sensitivity to low-velocity flows, while abscess stiffness was quantified using shear wave elastography. Most of the mature abscesses were characterized by a rounded core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. A treatable abscess was defined by its hypervascular rim and avascular core. Stiffness varied within the abscess but generally decreased over time. Abscess echogenicity, shape, stiffness and vascularity potentially provide features to identify lesions suitable for treatment.

Abscesses are walled-off collections of infected fluids containing pus and bacteria. They are often treated with percutaneous drainage in which a drainage catheter may be sutured in place for up to several weeks. Complications such as clogged drains or secondary infections require rehospitalization and wound management. Bacteria are susceptible to mechanical damage, and thus we hypothesize that histotripsy may be a potential new paradigm for treating abscesses noninvasively, without the need for long term catheterization and antibiotics. We developed a porcine animal model that recapitulates some of the features of human abscesses (including size and loculations). Boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses in this porcine model. Ultrasound imaging was used to evaluate abscess maturity, for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

BackgroundAbscess formation is a host defense mechanism to contain the spread of infection. Abscesses can affect any part of the body and are commonsequelaeto complications of trauma, surgery, systemic infections and other disease states. Most models for abscesses are in small animals. Pursuant to the goal of developing more advanced treatments for abscesses, we sought to develop a large animal model which would reasonably mimic a fluid-filled human abscess.MethodsDomestic swine were inoculated with a bimicrobial mixture ofBacteroides fragilis(B. fragilis) andEscherichia coli(E. coli) supplemented with an irritant (dextran). Inoculations were performed under ultrasound guidance in the muscle, subcutaneously or intradermally within the same animal. Fourteen days after inoculation, lesions were imaged with ultrasound, resected and prepared for histological evaluation.ResultsInjection of bimicrobial (aerobic and anaerobic) bacterial mixtures at multiple sites in a pig produced multiple lesions with histological features similar to encapsulated and multiloculated/multichamber abscesses often observed clinically in humans. Important salient features include the formation of a connective tissue capsule surrounding histologically nearly amorphous pus.ConclusionsThis paper provides the first description of a pig model for multiloculated abscesses. This animal model could potentially enable the evaluation of new technologies to replace or augment the current standard of care (image-guided percutaneous abscess drainage with antibiotics).

PURPOSE We aimed to demonstrate feasibility of the use of a dual-balloon infusion microcatheter for segmental/subsegmental drug-eluting bead transarterial chemoembolization (DEB-TACE). METHODS Over a 16-month period, 15 segmental and 21 subsegmental DEB-TACE procedures were attempted using a dual-balloon anti-reflux microcatheter (IsoFlow™ microcatheter, Vascular Designs Inc.) in 21 patients (15 males; median age, 61 years; range, 49-82 years) with hepatocellular carcinoma (Barcelona clinic liver cancer stage A [n=4]; B [n=12]; C [n=5]) with one to three tumors, median size of 3.4 cm (1.2-9 cm). Follow-up enhanced computed tomography or magnetic resonance imaging was obtained at one month then subsequently every three months for one year. Technical success was evaluated. Modified RECIST criteria was used for target tumor response assessment. Safety was evaluated by assessing for arterial injury and hepatic injury at the time of the procedure and subsequent evidence of complications and liver toxicity. RESULTS In 26 of the procedures, the segmental/subsegmental arteries were thought not to be easily selected with standard microcatheters due to the arterial branches being severely tortuous/angulated or atretic from prior TACE or anti-angiogenic therapy or could not be catheterized. Radiologic response assessment of treated tumors demonstrated 32% complete response, 19% partial response, 34% stable disease, and 15% progressive disease. No complications occurred. The median time to progression for the targeted tumors was 7 months (range, 3-12 months). CONCLUSION DEB-TACE, using this dual-balloon anti-reflux infusion microcatheter is feasible and safe.

With over 18 000 patients undergoing intermittent hemodialysis treatment in more than 350 dialysis centers, Turkey today has the fifth largest chronic hemodialysis patient population among European countries (1). In the United States, there are approximately 370 000 hemodialysis patients (2). Frequent thrombosis is well described in both dialysis arteriovenous (AV) grafts and fistulae (2). One and two-year patency rates for dialysis grafts have been reported to be 60%–80% and 50%–70%, respectively (2). This represents a major source of hospital admissions, increasing hospital costs and patient morbidity in most countries. Thrombosed fistulae and grafts can be declotted using pharmacomechanical techniques combining thrombolysis and thrombectomy, or by mechanical thrombectomy alone (3, 4). The medical literature suggests that technical success rates for thrombolysis of thrombosed fistulae ranges from 76%–96% (5–7). However, all declotting procedures carry a risk of distal arterial embolization and hemorrhagic complications (4). Large randomized controlled clinical trials evaluating thrombolysis and thrombectomy procedures for thrombosed dialysis grafts show a 3%–18% occurrence rate of adverse events (8–10). XCOIL™ (NexGen Medical Systems Inc.) is a new FDA-approved, catheter-based mechanical thrombectomy device (11) (Fig. 1). Preclinical animal studies have shown that XCOIL™ enables safe and effective percutaneous thrombectomy of soft acute and firm chronic thrombus in arteries and veins without the use of thrombolytics (11 ). The aim of this clinical study was to preliminarily evaluate the safety and effectiveness of XCOIL™ mechanical thrombectomy for the endovascular treatment of thrombosed AV grafts and fistulae. Figure 1. a, b Photograph (a) of fully assembled XCOIL™ mechanical thrombectomy device, including actuated loops, within the intravascular basket (Encapsulator™, NexGen Medical Systems Inc.). Bench-top demonstration of two different sized XCOIL TM loops ...

Induction of vascular hyperpermeability is one of the early vascular responses to radiation exposure and is considered to contribute to subsequent fibrosis and tissue injuries. However, the mechanism underlying radiation-induced hyperpermeability has not yet been clearly elucidated. Here, we provide experimental evidence indicating that mast cells contribute to the increase in vascular permeability for albumin in normal mouse skin after irradiation. Vascular permeability in the skin of C3H mice increased after 2, 15 and 50 Gy irradiation, peaked at 24 h after irradiation and gradually decreased thereafter to the baseline level within 3-10 days. Both the extent and duration of hyperpermeability were dose dependent. We found significant degranulation of mast cells in the skin after 15 Gy irradiation. To further investigate the role of mast cells in the radiation-induced increase in vascular permeability, we measured vascular permeability in the skin of mast cell-deficient mice (WW(v)) and their wild-type littermates at 24 h after irradiation. Vascular permeability in WW(v) mice did not change, whereas that in wild-type mice significantly increased after irradiation. There were no appreciable changes in the total tissue levels of vascular endothelial growth factor or endothelial nitric oxide synthase after 15 Gy irradiation and there was no detectable expression of inducible nitric oxide synthase. Collectively, these results show that exposure to radiation induces vascular hyperpermeability in a dose-dependent manner and that mast cells contribute to this process.

To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET. This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child–Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2. The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0–133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child–Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy. Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

We hypothesize that new insights into how cancers progress and respond to treatment will come from clinical trials that i) extensively characterize the molecular features of a patient’s cancer; ii) use results to predict drug susceptibilities; iii) treat in accordance with these predictions; and iv) learn from individual patient outcomes to iterate and improve over time. To investigate the feasibility of this type of clinical study, we launched the "Intensive Trial of OMics in Cancer" (ITOMIC) for patients with metastatic triple negative breast cancer (TNBC) (Clinicaltrials.gov ID: NCT01957514). Eligible patients have metastatic TNBC, are platinum-naive, and are scheduled to receive Cisplatin. Biopsies are performed under carefully controlled conditions prior to Cisplatin – starting all subjects on a common treatment path, and uncoupling the time needed for specimen analysis from immediate therapy. Biopsies are repeated upon completion of Cisplatin and following subsequent therapies. A subset of specimens is chosen for whole Exome Sequencing, deep sequencing of a panel of cancer associated genes, and RNA-sequencing. De-identified results are placed on a web-based server for analysis and discussed at a meeting of the ITOMIC tumor board. A report describing results and potential therapies is provided to the subject’s oncologist. Treatment decisions are left to the discretion of the oncologist. If a decision is taken to pursue treatments identified in our report we offer assistance in accessing those treatments. Ten patients have been screened and seven have enrolled. Subjects range in age from 40 to 77 years and all but one has received extensive prior treatment for metastatic TNBC. All seven underwent an initial set of biopsies, targeting between two and five metastatic sites. For most metastatic sites, multiple core needle passes are performed. All subjects tolerated the biopsies well without significant adverse events, and all started treatment with Cisplatin. Three subjects completed Cisplatin and underwent a second round of biopsies. Potential targets for therapy were identified in 5 of the first 6 subjects, and three subjects have received four predicted therapies: 1) a patient with somatic loss of BRCA1 and two linked FGFR2 activating mutations, who was treated first with Veliparib through a single-patient IND and then switched to Ponatinib which produced a partial response; 2) a patient with a novel missense ROS1 mutation treated with crizotinib; and 3) a patient with CYP3A4 copy gain treated with cyclophosphamide. Conclusion: Our early experience indicates that this approach is feasible and may increase the efficiency of learning from patients with advanced cancer. Citation Format: C Anthony Blau, Colin Pritchard, Michael O Dorschner, Sibel Blau, Brigham Mecham, Elisabeth Mahen, VK Gadi, Wayne Monsky, Kimberly Burton, Arturo Ramirez, Jackie Stilwell, Eric Kladjian, Carol Collins, Jeannine S McCune, William S Noble, Julie Gralow, Frank Senecal, Linda Dhaene, Nicole Kuderer, Jennifer Specht, Chaozhong Song, Carla Grandori, Nathan Price, Mary Goldman, Aime Radenbaugh, David Haussler, Jingchun Zhu. Assessing the safety and feasibility of efficient hypothesis testing in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-08-01.

Purpose To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. Methods and Materials A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. Results Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P Conclusions Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

To compare segmental radioembolization with segmental chemoembolization for localized, unresectable hepatocellular carcinoma (HCC) not amenable to ablation.In a single-center, retrospective study (2010-2015), 101 patients with 132 tumors underwent segmental radioembolization, and 77 patients with 103 tumors underwent segmental doxorubicin-based drug-eluting embolic or conventional chemoembolization. Patients receiving chemoembolization had worse performance status (Eastern Cooperative Oncology Group 0, 76% vs 56%; P = .003) and Child-Pugh class (class A, 65% vs 52%; P = .053); patients receiving radioembolization had larger tumors (32 mm vs 26 mm; P.001), more infiltrative tumors (23% vs 9%; P = .01), and more vascular invasion (18% vs 1%; P.001). Toxicity, tumor response, tumor progression, and survival were compared. Analyses were weighted using a propensity score (PS).Toxicity rates were low, without significant differences. Index and overall complete response rates were 92% and 84% for radioembolization and 74% and 58% for chemoembolization (P = .001 and P.001). Index tumor progression at 1 and 2 years was 8% and 15% in the radioembolization group and 30% and 42% in the chemoembolization group (P.001). Median progression-free and overall survival were 564 days and 1,198 days in the radioembolization group and 271 days and 1,043 days in the chemoembolization group (PS-adjusted P = .002 and P = .35; censored by transplant PS-adjusted P.001 and P = .064).Segmental radioembolization demonstrates higher complete response rates and local tumor control compared with segmental chemoembolization for HCC, with similar toxicity profiles. Superior progression-free survival was achieved.

About 16% of breast cancers fall into a clinically aggressive category designated triple negative (TNBC) due to a lack of ERBB2, estrogen receptor and progesterone receptor expression1-3. The mutational spectrum of TNBC has been characterized as part of The Cancer Genome Atlas (TCGA)4; however, snapshots of primary tumors cannot reveal the mechanisms by which TNBCs progress and spread. To address this limitation we initiated the Intensive Trial of OMics in Cancer (ITOMIC)-001, in which patients with metastatic TNBC undergo multiple biopsies over space and time5. Whole exome sequencing (WES) of 67 samples from 11 patients identified 426 genes containing multiple distinct single nucleotide variants (SNVs) within the same sample, instances we term Multiple SNVs affecting the Same Gene and Sample (MSSGS). We find that >90% of MSSGS result from cis-compound mutations (in which both SNVs affect the same allele), that MSSGS comprised of SNVs affecting adjacent nucleotides arise from single mutational events, and that most other MSSGS result from the sequential acquisition of SNVs. Some MSSGS drive cancer progression, as exemplified by a TNBC driven by FGFR2(S252W;Y375C). MSSGS are more prevalent in TNBC than other breast cancer subtypes and occur at higher-than-expected frequencies across TNBC samples within TCGA. MSSGS may denote genes that play as yet unrecognized roles in cancer progression.

Abscesses are infected walled-off liquid collections of pus and bacteria. They can affect any part of the body. Current treatment is typically limited to antibiotics, catheter drainage and hospitalization. Although bacteria can develop drug resistance, they are susceptible to mechanical damage from cavitation, as demonstrated in our prior in vitro work [Brayman et al., UMB 43, 1476–1485 (2017); Brayman et al., UMB 44, 1996–2008 (2018)]. Histotripsy is a pulsed focused ultrasound regime that generates localized cavitation and represents a potential new noninvasive treatment modality. Here, we present preliminary reports of inactivation of bacteria in a newly developed porcine abscess model. In this model, multiple large (2–4 cm) multiloculated bimicrobial abscesses can be formed at distinct sites in the same animal. The abscesses satisfy the true definition of an abscess and are formed within a relatively short period (2–4 weeks). The model was developed toward testing new abscess treatment technologies. We will describe the animal model, and preliminary results of histotripsy treatments in which liquefaction of the viscous pus contents and up to 5-fold reduction in bacteria viability were achieved. Funded in part by NIH NIBIB #R01EB019365 and R01GM122859.Abscesses are infected walled-off liquid collections of pus and bacteria. They can affect any part of the body. Current treatment is typically limited to antibiotics, catheter drainage and hospitalization. Although bacteria can develop drug resistance, they are susceptible to mechanical damage from cavitation, as demonstrated in our prior in vitro work [Brayman et al., UMB 43, 1476–1485 (2017); Brayman et al., UMB 44, 1996–2008 (2018)]. Histotripsy is a pulsed focused ultrasound regime that generates localized cavitation and represents a potential new noninvasive treatment modality. Here, we present preliminary reports of inactivation of bacteria in a newly developed porcine abscess model. In this model, multiple large (2–4 cm) multiloculated bimicrobial abscesses can be formed at distinct sites in the same animal. The abscesses satisfy the true definition of an abscess and are formed within a relatively short period (2–4 weeks). The model was developed toward testing new abscess treatment technologies. W...

Purpose To determine safety and efficacy of yttrium-90 ( 90 Y) transarterial radioembolization (TARE) in patients who have undergone chemoembolization for hepatocellular carcinoma. Materials and Methods A retrospective study identified 40 patients (median age 61 y; range, 44–84 y) who underwent 90 Y mapping angiography and had undergone ≥ one prior chemoembolizations. There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1–11.6 cm). The most common indications for changing to TARE were tumor progression (35/40; 86%) and development of portal vein thrombus (15/40; 37.5%). Results Of 40 patients, 29 (72.5%) underwent TARE; the most common reasons for not undergoing TARE were attenuated hepatic arteries (5/11), high pulmonary shunt (4/11), and poor arterial flow (2/11). Patients who underwent ≤ 4 chemoembolizations to the TARE target tended to be more likely to undergo TARE after mapping than patients who had > 4 chemoembolizations ( P = .056). Most common grade ≥ 3 toxicities were fatigue (9/29; 31%) and biochemical alterations (bilirubin [3/29; 10.3%], albumin [4/29; 13.8%], aspartate aminotransferase [5/29; 17.2%]). Of 27 patients treated with TARE with follow-up, responses were 11 (41%) complete response, 5 (19%) partial response, 2 (7%) stable disease, and 9 (33%) progressive disease. Median progression-free survival and overall survival were 90 days and 257 days. Conclusions TARE is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone > 4 chemoembolizations to the 90 Y target, feasibility of TARE tends to be decreased.

Purpose Thrombotic and embolic vascular occlusion represents a leading cause of morbidity and mortality. Currently available thrombectomy devices have limitations, including difficulty removing organized thrombus and clot fragmentation with distal embolization. A novel mechanical thrombectomy device (MTD), designed to remove both hard and soft thrombus without trauma to the blood vessel, was tested in preclinical porcine models evaluating efficacy, safety, and ease of use. Materials and Methods A total of 26 vessels in 14 pigs underwent mechanical thrombectomy with MTD. Thrombectomy was performed in nine superficial femoral arteries, eight subclavian arteries, five primary branches of the subclavian artery, lateral thoracic artery or the thyrocervical trunk, and four external carotids. Subacute organized fibrin-laden thrombus was injected into the arteries producing vascular occlusion. The MTD was then used for thrombectomy to restore patency and blood flow. Results Intact thrombus was retrieved from 24 of 26 of the vessels with a single pass of the MTD, resulting in complete restoration of patency in 21 vessels and partial patency in 4 vessels. In 8 cases that used an early design, the embolic material fragmented during withdrawal from the access sheath. In 4 procedures that used an early design, the MTD failed to deploy fully and the embolus was not completely captured. No intraprocedural complications or vascular damage occurred. Conclusions The present pilot studies demonstrate basic safety and efficacy of a novel MTD with design attributes suitable for retrieval of intact acute and organized chronic thrombus. The device has potential intracranial and peripheral utility.

To quantify contrast material enhancement of breast lesions scanned with dedicated breast computed tomography (CT) and to compare their conspicuity with that at unenhanced breast CT and mammography.Approval of the institutional review board and the Radiation Use Committee and written informed consent were obtained for this HIPAA-compliant study. Between September 2006 and April 2009, 46 women (mean age, 53.2 years; age range, 35-72 years) with Breast Imaging Reporting and Data System category 4 or 5 lesions underwent unenhanced breast CT and contrast material-enhanced breast CT before biopsy. Two radiologists independently scored lesion conspicuity for contrast-enhanced breast CT versus mammography and for contrast-enhanced breast CT versus unenhanced breast CT. Mean lesion voxel intensity was measured in Hounsfield units and normalized to adipose tissue intensity on manually segmented images obtained before and after administration of contrast material. Regression models focused on conspicuity and quantified enhancement were used to estimate the effect of pathologic diagnosis (benign vs malignant), lesion type (mass vs calcifications), breast density, and interradiologist variability.Fifty-four lesions (25 benign, 29 malignant) in 46 subjects were analyzed. Malignant lesions were seen significantly better at contrast-enhanced breast CT than at unenhanced breast CT (P.001) or mammography (P.001). Malignant calcifications (malignant lesions manifested mammographically as microcalcifications only, n = 7) were seen better at contrast-enhanced breast CT than at unenhanced breast CT (P.001) and were seen similarly at contrast-enhanced breast CT and mammography. Malignant lesions enhanced 55.9 HU +/- 4.0 (standard error), whereas benign lesions enhanced 17.6 HU +/- 6.1 (P.001). Ductal carcinoma in situ (n = 5) enhanced a mean of 59.6 HU +/- 2.8. Receiver operating characteristic curve analysis of lesion enhancement yielded an area under the receiver operating characteristic curve of 0.876.Conspicuity of malignant breast lesions, including ductal carcinoma in situ, is significantly improved at contrast-enhanced breast CT. Quantifying lesion enhancement may aid in the detection and diagnosis of breast cancer.

Background Limited data exist regarding the radiographic and histologic response of soft tissue sarcoma (STS) to neoadjuvant radiotherapy (RT). Methods Between February 2000 and January 2009, a total of 25 patients aged >16 years with intermediate- or high-grade primary STS of all sites were treated with neoadjuvant RT followed by definitive resection. Patients receiving chemoradiotherapy were excluded. Cross-sectional images obtained before and after RT as well as pathologic specimens were reviewed for maximal change in tumor diameter and percentage tumor necrosis, respectively. Clinicopathologic variables were analyzed for their association with pathologic and radiographic response. Results There were 18 extremity (72%) and 7 retroperitoneal (28%) tumors. Median maximal tumor size was 9 cm (range, 3.3–35 cm), and 88% were of high grade. There were 21 R0 resections (84%) and 4 R1 resections (16%). Radiographically, the median percentage change in tumor diameter was 0% (range, −25 to +86%). By Response Evaluation Criteria in Solid Tumors (RECIST), 5 patients demonstrated progressive disease, 20 demonstrated stable disease, and 0 demonstrated partial/complete response. The median pathologic percentage tumor necrosis was 30% (range, 5–100%). Two tumors (8%) demonstrated near-complete pathologic response (≥95% necrosis). Near-complete pathologic response was associated with favorable oncologic outcomes, although these associations were not statistically significant. Conclusions Radiologic and near-complete pathologic responses are rare events after preoperative RT for STS. Near-complete pathologic response may be a potentially meaningful surrogate marker for disease outcome and is not predicted by RECIST response. Knowledge of these historical response rates is important for the evaluation of novel neoadjuvant therapies for patients with STS.

The etiology of arteriovenous (AV) malformations remains incompletely understood. Two cases of acquired AV malformations wholly located within the thrombosed lumen of the femoral and external iliac veins are presented here. The patients presented with symptoms of high venous pressure: pigmented skin and chronic pain. Such AV malformations have been rarely described in the extracranial circulation. The associated pain was successfully treated with catheter-based embolization of the lesions. The induction of the AV malformations in the peripheral circulatory system raises questions regarding the nature of angiogenesis and its possible triggers.

Congenital vascular anomalies of pelvis and lower limb arteries are rare. During embryologic development, the sciatic artery represents the dominant supplier of blood to the lower limb. The external iliac and femoral arteries appear later in the process and take over as the sciatic artery regresses. Failure of the sciatic artery to regress creates a persistent sciatic artery malformation. Failure of the external iliac artery to properly bud may lead to similar vascular malformations. The authors present a patient with atresia of the left external iliac artery with an associated atresia of the left common iliac vein, duplication of the infrarenal inferior vena cava, and absence of the left S1 bony arch. The left-sided single iliac artery supplies both pelvic structures and the lower limb. The "pelvic" external iliac artery may result from embryologic budding at a lower segmental level than the usual fifth lumbar segmental artery. This combination of anomalies suggests an abnormality of segmentation on left at the first sacral level.

Intra- and extra-muscular hematomas result from repetitive injury as well as sharp and blunt limb trauma. The clinical consequences can be serious, including debilitating pain and functional deficit. There are currently no short-term treatment options for large hematomas, only lengthy conservative treatment. The goal of this work was to evaluate the feasibility of a high intensity focused ultrasound (HIFU)-based technique, termed histotripsy, for rapid (within a clinically relevant timeframe of 15-20 min) liquefaction of large volume (up to 20 mL) extra-vascular hematomas for subsequent fine-needle aspiration. Experiments were performed using in vitro extravascular hematoma phantoms-fresh bovine blood poured into 50 mL molds and allowed to clot. The resulting phantoms were treated by boiling histotripsy (BH), cavitation histotripsy (CH) or a combination in a degassed water tank under ultrasound guidance. Two different transducers operating at 1 MHz and 1.5 MHz with f-number = 1 were used. The liquefied lysate was aspirated and analyzed by histology and sized in a Coulter Counter. The peak instantaneous power to achieve BH was lower than (at 1.5 MHz) or equal to (at 1 MHz) that which was required to initiate CH. Under the same exposure duration, BH-induced cavities were one and a half to two times larger than the CH-induced cavities, but the CH-induced cavities were more regularly shaped, facilitating easier aspiration. The lysates contained a small amount of debris larger than 70 μm, and 99% of particulates were smaller than 10 μm. A combination treatment of BH (for initial debulking) and CH (for liquefaction of small residual fragments) yielded 20 mL of lysate within 17.5 minutes of treatment and was found to be most optimal for liquefaction of large extravascular hematomas.

The purpose of this study was to determine whether the administration of liposomal doxorubicin before radiofrequency ablation increases coagulation more than radiofrequency alone in focal hepatic tumors.Fourteen focal hepatic tumors (diameter: mean +/- SD, 4.0+/-1.8 cm) in 10 patients (colorectal cancer, n = 3 patients; hepatocellular carcinoma, n = 4; neuroendocrine tumor, n = 2; breast cancer, n = 1) were treated with internally cooled radiofrequency ablation. In addition to undergoing radiofrequency, five patients (n = 7 lesions) were randomly assigned to receive 20 mg of IV doxorubicin in a long-circulating stealth liposome carrier (Doxil) 24 hr before ablation. Contrast-enhanced helical CT was performed immediately (within 30 min) after radiofrequency ablation (baseline) and 2-4 weeks after ablation. The volume of induced coagulation was measured by three-dimensional reconstruction techniques, and the measurements were compared.For tumors treated with radiofrequency alone, the volume of the thermal lesion had decreased 12-24% (mean +/- SD, 82.5% +/- 4.4% of initial volume) at 2-4 weeks after ablation. By comparison, increased tumor destruction at 2-4 weeks after ablation was observed for all lesions treated with combined Doxil and radiofrequency (p0.001). Six lesions increased 24-36% in volume, and coagulation surrounding a small colorectal metastasis increased 342%. No coagulation was identified in four unablated control lesions in the two patients receiving Doxil alone.Our pilot clinical study suggests that adjuvant Doxil chemotherapy increases tumor destruction compared with radiofrequency ablation therapy alone in a variety of focal hepatic tumors. Optimization of this synergistic strategy may ultimately allow improved clinical efficacy and outcome.

To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model.R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied.Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation.Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.

Locoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC. This retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients. Ablation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001). Ablation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100–300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: ( i ) spatially, by growing tumors in subcutaneous or cranial locations and ( ii ) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 μm. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: ( i ) delivery may be less efficient in cranial tumors than in subcutaneous tumors, ( ii ) delivery may be reduced during tumor regression induced by hormonal ablation, and ( iii ) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide.1,2 Approximately 37,000 men and women had a new diagnosis of HNSCC in 2011 in the United States.3 The 5-year survival rate is only 50% to 60%.1 Most patients with HNSCC typically present with advanced disease in the clinic despite the fact that oral or pharyngeal tumors are easily identifiable within the mouth and throat by direct visualization or simple awake endoscopy.4,5 Given the advanced stage of oral carcinomas at detection, current treatment approaches such as radiotherapy and surgical resection can result in substantial morbidity and impairment of speech, swallowing, taste, and facial appearance.6 As such, there is an urgent clinical need for techniques that allow for early diagnosis, optimal staging, and restaging and for monitoring responses following therapy for HNSCC. Ultrasound (US) imaging is one such technique currently used for the diagnosis, assessment, and surgical management of HNSCC.7–10 The corresponding US probes, typically with 5–15-MHz transducers, provide sufficient imaging penetration depth but are constrained by limited spatial resolution, which may hamper their effectiveness in detecting neoplastic features characteristic of HNSCC such as early invasive growth and disruptions of subepithelial layers and the basement membrane in suspected lesions. Other imaging modalities such as optical coherence tomography have been developed to overcome the resolution limitations associated with clinical US imaging. Studies in animal models and patients have yielded images of suspicious oral lesions with axial and lateral resolutions of less than 10 μm, allowing for the visualization of individual tissue layers of the oral mucosa. The spatial resolution afforded by optical coherence tomography allows for the detection of precancerous changes such as epithelial dysplasia in addition to the disruption of healthy tissue layers associated with more advanced neoplastic stages. However, optical coherence tomography is limited to a superficial interrogation of tissue surfaces with a maximum penetration depth ranging from 1 to 3 mm, with commercial systems providing a penetration depth of 1.5 mm and an imaging focal depth of 1.0 mm.11–14 High-frequency (>20-MHz) ultrasound backscatter microscopy (UBM) systems may show promise for oral cancer detection by producing high-resolution images at a reasonable penetration depth that may better delineate tissue structures. Specifically, with operating frequencies of 40 to 60 MHz, a spatial resolution of less than 0.1 mm and up to 6 mm of depth penetration with reasonable contrast to noise ratios can be obtained from these systems.15–18 Commercial systems with these characteristics (eg, Vevo series; VisualSonics, Toronto, Ontario, Canada) have also now become readily available.18 The sizes of the imaging probes of these commercial systems, however, has made their use in oral applications impractical. Recently, our group built a compact and portable high-frequency (41-MHz) UBM system that uses a single-element transducer.19 The size and shape of the probe (specifications in “Materials and Methods”) render it suitable for interrogation of oral tissue in vivo in human patients at up to 6 to 7 mm in depth with high axial resolution (

Ultrasound imaging has long since been used for visualization of anatomic structures for disease diagnosis and guidance during therapeutic procedures. Benefits of Ultrasound include a lack of ionizing radiation and real-time dynamic imaging. It is also the least expensive, most widely available imaging technology. In gray scale ultrasonic imaging, the signals which form the image result from reflection and scattering of soundwaves where there are differences in the characteristic tissue impedances. Ultrasonography has changed little since the 1970s. Only basic anatomic information is obtained with the modality such as: organ length, cortical thickness, collecting system or ductal dilatation are assessed. Doppler Ultrasound allows assessment of vascular physiology including blood flow velocity, which in addition to anatomic images can be used to determine the hemodynamic physiologic significance of stenosis. Resistive Index (peak systolic velocity end diastolic velocity)/peak systolic velocity) a quantitative measure of blood flow, vascular resistance/compliance, is commonly used in the diagnosis of renal dysfunction [1].

4084Background: Transarterial chemoembolization (TACE) remains the standard of care for localized, surgically unresectable hepatocellular carcinoma (HCC). However, yttrium-90 radioembolization (Y90...

Malignancies may cause urinary tract obstruction, which is often relieved with placement of a percutaneous nephrostomy tube, an internal double J nephro-ureteric stent (double J), or an internal external nephroureteral stent (NUS). We evaluated the affect of these palliative interventions on quality of life (QoL) using previously validated surveys.Forty-six patients with malignancy related ureteral obstruction received nephrostomy tubes (n = 16), double J stents (n = 15), or NUS (n = 15) as determined by a multidisciplinary team. QoL surveys were administered at 7, 30, and 90 days after the palliative procedure to evaluate symptoms and physical, social, functional, and emotional well-being. Number of related procedures, fluoroscopy time, and complications were documented. Kruskal-Wallis and Friedman's test were used to compare patients at 7, 30, and 90 days. Spearman's rank correlation coefficient was used to assess correlations between clinical outcomes/symptoms and QoL.Responses to QoL surveys were not significantly different for patients receiving nephrostomies, double J stents, or NUS at 7, 30, or 90 days. At 30 and 90 days there were significantly higher reported urinary symptoms and pain in those receiving double J stents compared with nephrostomies (P = 0.0035 and P = 0.0189, respectively). Significantly greater fluoroscopy time was needed for double J stent-related procedures (P = 0.0054). Nephrostomy tubes were associated with more frequent minor complications requiring additional changes.QoL was not significantly different. However, a greater incidence of pain in those receiving double J stents and more frequent tube changes in those with nephrostomy tubes should be considered when choosing palliative approaches.

This investigation aimed to evaluate patient characteristics and procedural factors associated with abnormal nephrograms encountered on noncontrast computed axial tomography (CAT) obtained 24-h after transarterial chemoembolization (TACE) for primary and metastatic hepatic malignancies. Sixty hepatic chemoembolization procedures were performed in 29 patients who had a median age of 63 years (range 42–79). The male-to-female ratio was 16:13. Noncontrast CAT scans were obtained approximately 24 h after TACE as part of our institutional protocol and were examined for persistent renal nephrograms. These findings were compared with clinical and procedural parameters to determine whether there was any association with these factors or with the occurrence of acute renal failure (ARF). Abnormally persistent CAT nephrograms were observed 24 h after 28 of 60 (46.7%) TACE procedures, of which 14 (23.3%) were persistent, bilaterally dense, global nephrograms, and 14 (23.3%) were small, wedge-shaped, and focal nephrograms. The change in serum creatinine from baseline to 24 h was significantly greater (p = 0.031) in the global nephrogram group. The presence of cirrhosis, Child-Pugh score, procedure time, baseline renal insufficiency, and lower periprocedural mean arterial blood pressure were also statistically significantly associated with the occurrence of bilateral globally dense nephrograms. The procedure time was statistically significantly associated with the occurrence of wedge-like focally persistent nephrograms. Global, persistently dense nephrograms and wedge-shaped focally persistent nephrograms are not infrequently observed after TACE. Persistent global nephrograms can be an important clinical indicator of ARF. The wedge nephrogram may represent focal renal ischemia.

Purpose To develop a new technique for percutaneous removal of common bile duct (CBD) gallstones by using a pneumatic lithotripter with a XCOIL encapsulator (XE) and retractor (XR) system. Materials and Methods For in-vitro confirmation, a 6.0mm glass tube was shaped to simulate the cystic duct and CBD of pigs. Human gallstone was placed into the tube. An 11Fr custom balloon introducer sheath (BIS) was positioned close to the gallstone, and then inflated to occlude the proximal tube. An XE and XR system was advanced through the BIS into the tube, to catch the gallstone by pulling XR back into the XE. The stone was restricted within the XE by closing the distal XE end via a string. A 1.0mm lithotripter probe was manually-curved according to the glass tube shape and then advanced into the XE through the BIS, where the gallstone was shocked. Fragments were then extracted from the tube with the XE. Lithotripsy procedures were repeated for 6 times. The shock numbers, the skin-to-skin lithotripsy time and fragment sizes were recorded. For in-vivo validation, via a transcystic approach, human gallstones were positioned into CBDs of three pigs through a 16Fr introducer. Under fluoroscopy, an 11Fr BIS was placed into CBD to break and remove the gallstones with the same procedures as developed from the in-vitro experiment. Pre- and post-cholangiographies were obtained to confirm the successes of the gallstone placement, breaking, and removal. After the experiment, the pigs were euthanized and CBDs were harvested for histology. Results Of the in-vitro experiment, average 9.5±4.2 shocks were required to break gallstones. The average skin-to-skin lithotripsy time was 6'10". All stones were successfully broken, with the average maximal length of the gallstone fragments at 2.1±0.3mm compared to the pre-lithotripsy stone length at 5.3±0.2 mm (p Conclusion The new XCOIL-assisted percutaneous pneumatic lithotripsy is feasible and safe for CBD gallstones breaking and removal, which establishes groundwork for its further clinical application.

TPS333 Background: Despite effective local therapy, patients with locally advanced extremity soft tissue sarcoma (ESTS) are at high risk for distant failure and demise. Novel therapies for this gro...