Prostatic Artery Embolization in Patients with Refractory Lower Urinary Tract Symptoms after a Prior Minimally Invasive Surgical Treatment.

The purpose of this study was to report on prostatic artery embolization (PAE) outcomes in patients with refractory or recurrent lower urinary tract symptoms (LUTSs) due to benign prostatic hyperplasia (BPH) who had previously undergone a minimally invasive surgical technique (MIST). A single-center retrospective study identified 16 eligible patients. Baseline prostate volume at the time of PAE was 112.9 mL (SD ± 52.7). There were no adverse events throughout the follow-up period. There was significant improvement in International Prostate Symptom Score and quality of life from baseline of 23.5 (SD ± 5.1) and 4.9 (SD ± 0.9), respectively, to the last follow-up of 11.6 (SD ± 7.2) and 2 (SD ± 1.6), respectively. There was nonsignificant improvement in sexual function after PAE compared with baseline after MIST. PAE can be a safe and effective treatment in patients who have undergone prior MIST without negatively impacting erectile or ejaculatory function.

Treatment of Unicameral Bone Cysts Utilizing the Sclerograft™ Technique.

PURPOSE: To evaluate the Sclerograft™ procedure, which is an image-guided, minimally invasive approach of chemical sclerotherapy followed by bone grafting of unicameral bone cysts (UBC). MATERIALS AND METHODS: A retrospective evaluation from August 2018 through August 2023 was performed at a single institution on patients that underwent the Sclerograft™ procedure for UBCs. Radiographic healing was evaluated utilizing the Modified Neer Classification. Two different regenerative grafts, CaSO4-CaPO4 and HA-CaSO4 were utilized. A total of 50 patients were evaluated with 41 patients grafted with CaSO4-CaPO4 and 9 patients grafted with HA-CaSO4. RESULTS: The average age of the patient was 12.1 years with an average radiographic follow-up of 14.5 months. Average cyst size was 5.5 cm in the largest dimension and average cyst volume was 20.2 cc. 42 out of 50 (84%) showed healed cysts (Modified Neer Class 1) on the most recent radiograph or MRI. Recurrences occurred on average at 7.2 months. Activity restrictions were lifted at 3-4.5 months post-procedure. Cyst stratification by size did not show a difference in recurrence rates (p = 0.707). There was no significant difference in recurrence rate between lesions abutting the physis compared to those that were not abutting the physis (p = 0.643). There were no major complications. CONCLUSIONS: The Sclerograft™ procedure is an image-guided approach to treating unicameral bone cysts, utilizing chemical sclerosis and regenerative bone grafting. The radiographic healing of cysts compares favorably to open curettage and grafting as determined utilizing previously published trials.

Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo-Immuno-Embolization for the Treatment of Hepatocellular Carcinoma.

Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.

Controversies in Prostate Artery Embolization: Future Best Practice.

Prevalence of lower urinary tract symptoms secondary to benign prostatic hyperplasia is correlated with age. Men seeking treatment options with a low side effect profile often turn to prostate artery embolization (PAE). PAE continues to be refined with advanced tools and optimized techniques. Nonetheless, there exist controversies in terms of best practices for the management of lower urinary track symptoms (LUTS) with PAE. These controversies are essential for medical progress. Herein we suggest best practices moving forward based on currently available data. Given extensive safety data, we recommend PAE be considered alongside medical management and as a precursor to surgery. Given demonstrated efficacy across gland sizes, PAE can be performed in a single session, ideally in a hybrid angio-CT suite, without preoperative cross-sectional imaging. PAE should be initially performed with 300- to 500-µm size particles, and instead consider exploring other particles and sizes for repeat PAE. Finally, PAE can also be considered as first-line option for recurrent disease given the efficacy and excellent safety profile. This article is not meant to purport a dogma, but rather to serve as a guide to the experienced practitioner in challenging his or her own biases when performing PAE.

Role of interventional oncology in hepatocellular carcinoma: Future best practice beyond current guidelines.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Liver transplant remains the goal of curative treatment, but limited supply of organs decreases accessibility and prolongs waiting time to transplantation. Therefore, interventional oncology therapies have been used to treat the majority of HCC patients, including those awaiting transplant. The Barcelona Clinic Liver Cancer (BCLC) classification is the most widely used staging system in management of HCC that helps allocate treatments. Since its inception in 1999, it was updated for the fifth time in November 2021 and for the first time shaped by expert opinions outside the core BCLC group. The most recent version includes additional options for early-stage disease, substratifies intermediate disease into three groups, and lists alternates to Sorafenib that can double the expected survival of advanced-stage disease. The group also proposed a new BCLC staging schema for disease progression, and endorsed treatment stage migration (TSM) directly into the main staging and treatment algorithm. This article reviews the recent developments underlying the current BCLC guidelines and highlights ongoing research, particularly involving radioembolization, that will shape future best practice.

Preoperative portal vein recanalization-transjugular intrahepatic portosystemic shunt for chronic obliterative portal vein thrombosis: Outcomes following liver transplantation.

High-grade portal vein thrombosis (PVT) is often considered to be a technically challenging scenario for liver transplantation (LT) and in some centers a relative contraindication. This study compares patients with chronic obliterative PVT who underwent portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) and subsequent LT to those with partial nonocclusive PVT who underwent LT without an intervention. This institutional review board-approved study analyzed 49 patients with cirrhosis with PVT from 2000 to 2020 at our institution. Patients were divided into two groups, those that received PVR-TIPS due to anticipated surgical challenges from chronic obliterative PVT and those who did not because of partial PVT. Demographic data and long-term outcomes were compared. A total of 35 patients received PVR-TIPS while 14 did not, with all receiving LT. Patients with PVR-TIPS had a higher Yerdel score and frequency of cavernoma than those that did not. PVR-TIPS was effective in decreasing portosystemic gradient (16 down to 8 mm HG; p < 0.05). Both groups allowed for end-to-end anastomoses in >90% of cases. However, veno-veno bypass was used significantly more in patients who did not receive PVR-TIPS. Additionally, patients without PVR-TIPS required significantly more intraoperative red blood cells. Overall survival was not different between groups. PVR-TIPS demonstrated efficacy in resolving PVT and allowed for end-to-end portal vein anastomoses. PVR-TIPS is a viable treatment option for chronic obliterative PVT with or without cavernoma that simplifies the surgical aspects of LT.

Extrahepatic Applications of Yttrium-90 Radioembolization.

While initially described and now accepted as treatment for primary and secondary malignancies in the liver, radioembolization therapy has expanded to include treatment for other disease pathologies and other organ systems. Advantages and limitations for these treatments exist and must be compared against more traditional treatments for these processes. This article provides an overview of the current applications for radioembolization outside of the liver, for both malignant and nonmalignant disease.

Yttrium-90 Radioembolization in the VX2 Rabbit Model: Radiation Safety and Factors Influencing Delivery Efficiency.

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (90Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1-63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 µSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. 90Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a "how-to" for the setup of a preclinical 90Y laboratory are included to support future translational research.

Duramycin radiosensitization of MCA-RH 7777 hepatoma cells through the elevation of reactive oxygen species.

OBJECTIVE: The objective of this study is to explore the radiosensitization effects of duramycin against the liver cancer hepatoma cells and relationship to reactive oxygen species (ROS) generation. MATERIALS AND METHODS: MCA-RH 7777 cells were treated with various combinations of duramycin concentrations and radiation doses. After the treatment, cell viabilities were determined by a cell proliferation assay; intracellular ROS levels were detected with the flow cytometric method. RESULTS: MCA-RH 7777 cell viability was found significantly reduced after combining duramycin and radiation exposure (comparing to that of either treatment alone). Increased intracellular ROS levels were observed in cells treated with combinations of duramycin and radiation. CONCLUSION: Duramycin increased the intracellular ROS generation and also increased the radiosensitivity of MCA-RH 7777 cells.

TIPS for Adults Without Cirrhosis With Chronic Mesenteric Venous Thrombosis and EHPVO Refractory to Standard-of-Care Therapy.

BACKGROUND AND AIMS: Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy. APPROACH AND RESULTS: Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%. CONCLUSIONS: TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.

Yttrium-90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation.

PURPOSE: To investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model. MATERIALS AND METHODS: Fourteen male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic prostatic artery catheterization. Yttrium-90 (90Y) microspheres (TheraSphere; Boston Scientific, Marlborough, Massachusetts) were delivered to 1 prostatic hemigland (dose escalation from 60 to 200 Gy), with the contralateral side serving as a control. Assessments for adverse events were performed throughout the follow-up (Common Terminology Criteria for Adverse Events v5.0). Positron emission tomography/magnetic resonance (MR) imaging provided a confirmation after the delivery of absorbed-dose distribution. MR imaging was performed before and 3, 20, and 40 days after RE. Tissue harvest of the prostate, rectum, bladder, urethra, penis, and neurovascular bundles was performed 60 days after RE. RESULTS: All the animals successfully underwent RE. Positron emission tomography/MR imaging demonstrated localization to and good coverage of only the treated hemigland. No adverse events occurred. The MR imaging showed a significant dose-dependent decrease in the treated hemigland size at 40 days (25%-60%, P < .001). No extraprostatic radiographic changes were observed. Necropsy demonstrated no gross rectal, urethral, penile, or bladder changes. Histology revealed RE-induced changes in the treated prostatic tissues of the highest dose group, with gland atrophy and focal necrosis. No extraprostatic RE-related histologic findings were observed. CONCLUSIONS: Prostate 90Y RE is safe and feasible in a canine model and leads to focal dose-dependent changes in the gland without inducing unwanted extraprostatic effects. These results suggest that an investigation of nonoperative prostate cancer is warranted.

Comparing Real World, Personalized, Multidisciplinary Tumor Board Recommendations with BCLC Algorithm: 321-Patient Analysis.

PURPOSE: To evaluate hepatocellular carcinoma (HCC) treatment allocation, deviation from BCLC first-treatment recommendation, and outcomes following multidisciplinary, individualized approach. METHODS: Treatment-naïve HCC discussed at multidisciplinary tumor board (MDT) between 2010 and 2013 were included to allow minimum 5 years of follow-up. MDT first-treatment recommendation (resection, transplant, ablation, transarterial radioembolization (Y90), transarterial chemoembolization, sorafenib, palliation) was documented, as were subsequent treatments. Overall survival (OS) analyses were performed on an intention-to-treat (ITT) basis, stratified by BCLC stage. RESULTS: Three hundred and twenty-one patients were treated in the 4-year period. Median age was 62 years, predominantly male (73%), hepatitis C (41%), and Y90 initial treatment (52%). There was a 76% rate of BCLC-discordant first-treatment. Median OS was not reached (57% alive at 10 years), 51.0 months, 25.4 months and 13.4 months for BCLC stages A, B, C and D, respectively. CONCLUSION: Deviation from BCLC guidelines was very common when individualized, MDT treatment recommendations were made. This approach yielded expected OS in BCLC A, and exceeded general guideline expectations for BCLC B, C and D. These results suggest that while guidelines are helpful, implementing a more personalized approach that incorporates center expertise, patient-specific characteristics, and the known multi-directional treatment allocation process, improves patient outcomes.

Does significantly elevated lung shunt fraction (LSF >20%) promote extrahepatic progression in patients with hepatocellular carcinoma treated with radioembolization?

PURPOSE: Radioembolization with yttrium-90 (Y-90) is an effective locoregional therapy for primary and metastatic liver tumors, but its use is restricted or contraindicated for patients with elevated lung shunt fraction (LSF) because of an increased risk of developing pulmonary adverse events, including but not limited to radiation pneumonitis. Elevated LSF is also thought to be correlated with liver tumor progression and metastases. METHODS: In this retrospective cohort study, we examine rates of metastasis development, rates of adverse events and overall survival (OS) in 23 patients with hepatocellular carcinoma (HCC) and elevated LSF >20% on Tc-99 m macroaggregated albumin scan treated with Y-90 radioembolization at our institution from 2005 to 2016. To minimize confounding variables, patients with baseline extrahepatic metastases or portal vein tumor thrombosis were excluded. Kaplan-Meier estimates were performed for OS and time to development of metastases. RESULTS: No patient developed clinical and imaging signs of radiation pneumonitis. Median intention to treat OS from day of radioembolization was 21.3 months; median censored OS was 14.7 months. Five out of 23 patients (22%) developed at least one metastasis during follow-up, for an incidence of 20 per 1000 patient-years (compared to the historical rate of 6 per 1000 patient-years for HCC patients in general). CONCLUSION: HCC patients with LSF >20% treated with Y-90 radioembolization have acceptable toxicities and appear to have a rate of extrahepatic tumor development (22%) higher than expected for patients with HCC.

Liver Transplantation Following Yttrium-90 Radioembolization: 15-Year Experience in 207-Patient Cohort.

BACKGROUND AND AIMS: Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS: Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P < 0.0001). For patients with UNOS T2 treated during the study period, 5.2% dropped out because of disease progression. CONCLUSIONS: Y90 is an effective treatment for HCC in the setting of bridging/downstaging to LT. Patients who achieved extensive or complete necrosis had better RFS, supporting the practice of neoadjuvant treatment before LT.

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures.

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca2+ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.