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Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that "personalizing" dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

To assess the liver function trends in patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC] Stage B) hepatocellular carcinoma (HCC) who underwent yttrium-90 transarterial radioembolization (TARE) in response to a growing concern that liver-directed therapies negatively affect liver function and prevent patients with HCC from systemic therapy candidacy. An HCC/TARE database (2004–2017) was retrospectively reviewed. Patients with BCLC Stage B/Child–Pugh (CP)-A HCC with laboratory test and imaging data at baseline and for at least 1 month after TARE were included. Follow-ups were at 3-month intervals. CP stage was assessed at each time point. End points included time to persistent CP-B status, time to CP-C status, and median overall survival (OS). Time–to–end point analyses were performed using the Kaplan–Meier method. Seventy-four patients (80% men, with a mean age of 63 years) with mostly (62%) bilobar disease underwent 186 TARE treatments (median, 2; range, 1–8). The median time to second TARE was 2.3 months (range, 1.7–6.4 months), and the median times to third and fourth TAREs were 11.7 months (range, 7.5–15 months) and 17.3 months (range, 11.5–23.1 months), respectively. Forty-three (58%) patients developed persistent CP-B HCC at a median time of 15.4 months (95% CI, 9.2–25.3 months); 17 (23%) patients developed CP-C HCC at a median time of 87.2 months (95% CI, 39.8–136.1 months). The median OS censored to transplantation was 30.4 months (95% CI, 22.7–37.4 months). On univariate and multivariate analyses, baseline albumin was a significant prognosticator of OS, whereas baseline albumin and bilirubin were significant prognosticators of time to persistent CP-B HCC and time to CP-C HCC. In patients with CP-A HCC who underwent TARE for BCLC Stage B HCC, the median time to persistent CP-B HCC was 15.4 months. These findings indicate that patients would be candidates for systemic therapy at progression if indicated. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of yttrium-90 (90Y) radiation segmentectomy (RS) in the treatment of oligometastatic secondary hepatic malignancies. This institutional review board–approved retrospective study evaluated 16 patients with oligometastatic secondary hepatic malignancies who were treated with RS. The median patient age was 61.9 years (range, 38.6–85.7 years). Of the 16 patients, 11 (68.8%) presented with solitary lesions. The median index tumor size was 3.1 cm (95% CI, 2.3–3.9). Primary outcomes were evaluation of clinical and biochemical toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, and imaging response using Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary outcomes were time to progression (TTP) and overall survival (OS) as estimated by the Kaplan-Meier method. Clinical Grade 3 toxicities were limited to 1 (6.7%) patient who experienced fatigue, abdominal pain, nausea, and vomiting. Biochemical Grade 3 toxicities occurred in 1 (6.7%) patient who experienced lymphopenia. No Grade 4 clinical or biochemical toxicities were identified. Disease control was achieved in 14 (93.3%) of 15 patients. The median TTP of the treated tumor was 72.9 months (95% CI, 11.2 to no estimate). The median OS was 60.9 months (95% CI, 24.7 to no estimate). 90Y RS displayed an excellent safety profile and was effective in achieving a high disease control rate in the treatment of oligometastatic secondary hepatic malignancies. [Display omitted] [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model.Materials and Methods: White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67).Results: At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8-55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec-1 and decreased to 4.48 ± 9.00sec-1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071).Conclusion: The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile.Materials and Methods: This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method.Results: The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively.Conclusions: Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation. [ABSTRACT FROM AUTHOR]

The future of general surgery of children as practiced in District General (DGHs) and Rural General Hospitals (RGHs) by adult general surgeons and urologists is uncertain. It is likely that this is because of a combination of the overall trend towards specialization, concerns about clinical risk; uncertainty within the profession about the behavior of the regulator and criminal justice system when considering cases of alleged incompetence; reduced and more targeted training time, curriculum changes, and perhaps a concern by other specialties regarding the ability of DGH and RGH surgeons to provide a safe service. The impact of this on regional pediatric surgical units (RPSUs) is however considerable. While transfer of some conditions such as infantile hypertrophic pyloric stenosis and intussusception is justifiable, transfer of others such as undescended testis and suspected torsion is not. Close communication between regional specialists and local generalists, preferably in the setting of a formal network, together with a change in the priorities of local medical and nonmedical managers and cooperation between competing Trusts is required. Strategies for dealing with the problem are available but require a change in management and National Health Service (NHS) ethos to enact effectively. Adherence to evidence-based best practice with the help of the "Getting It Right First Time (GIRFT)" initiative is vital and, together with targeted publicity and encouragement, the trend may not be irreversible. Level V. [ABSTRACT FROM AUTHOR]

Multimodal-imaging probes offer a novel approach, which can provide detail diagnostic information for the planning of image-guided therapies in clinical practice. Here we report targeted multimodal Nd 3+ -doped upconversion nanoparticle (UCNP) imaging reporters, integrating both magnetic resonance imaging (MRI) and real-time upconversion luminescence imaging (UCL) capabilities within a single platform. Nd 3+ -doped UCNPs were synthesized as a core–shell structure showing a bright visible emission upon excitation at the near infrared (minimizing biological overheating and increasing tissue penetration depth) as well as providing strong MRI T2 contrast (high r 2 /r 1 ratio). Transcatheter intra-arterial infusion of Nd 3+ -doped UCNPs conjugated with anti-CD44-monoclonal antibody allowed for high performance in vivo multimodal UCL and MR imaging of hepatocellular carcinoma (HCC) in an orthotopic rat model. The resulted in vivo multimodal imaging of Nd 3+ doped core-shell UCNPs combined with transcatheter intra-arterial targeting approaches successfully discriminated liver tumors from normal hepatic tissues in rats for surgical resection applications. The demonstrated multimodal UCL and MRI imaging capabilities of our multimodal UCNPs reporters suggest strong potential for in vivo visualization of tumors and precise surgical guidance to fill the gap between pre-procedural imaging and intraoperative reality. [ABSTRACT FROM AUTHOR]

A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. [ABSTRACT FROM AUTHOR]

Purpose: To test whether iron oxide (IO)-containing yttrium aluminosilicate (YAS) microparticles (MPs) can generate localized therapeutic hyperthermia (≥ 43°C) when injected intratumorally in an animal model of liver cancer and whether MP distributions could be visualized with magnetic resonance (MR) imaging.Materials and Methods: Twenty-one Sprague-Dawley rats implanted with N1-S1 liver tumors were assigned to alternating magnetic field (AMF) exposure following intratumoral injection with IO-YAS MPs (n = 7), sham surgery (n = 7), or baseline iron quantification (n = 7). Three fiberoptic probes allowed spatial and temporal monitoring of temperatures during 24 minutes of AMF exposure. T2-weighted turbo spin-echo MR imaging was performed within 1 hour after the procedure to detect signal voids caused by IO-YAS deposition. Hematoxylin and eosin-stained pathologic slides were also obtained, and the presence of IO-YAS was evaluated with inductively coupled plasma optical emission spectroscopy.Results: Following AMF exposure, intratumoral temperatures after IO-YAS MP injection achieved therapeutic hyperthermia whereas those after sham surgery did not (46.6°C ± 1.3 vs 36.8°C ± 0.4; P < .0001). Within the treated group, the normal hepatic parenchyma (NHP) and rectal temperatures were 37.4°C ± 0.9 and 36.5°C ± 1.0 (P = .0809) at the conclusion of AMF exposure, respectively. A T2-weighted signal void at the tumor site was observed in all seven treated animals, and intratumoral IO-YAS was visualized on subsequent histopathologic examination in each case. The mean ratio of tumor:NHP Fe concentrations attributable to IO-YAS MPs was 108:1.Conclusions: AMF exposure of intratumoral IO-YAS MPs generates localized therapeutic hyperthermia in an animal model of liver cancer. MR detectability and potential for combination brachytherapy warrants further investigation for thermoradiotherapy in liver cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Primary aorto-enteric fistula (PAEF) is a life threatening, spontaneous erosion and communication of the aorta and intestinal tract. Unlike secondary AEF, which occur following aortic surgery, they are extremely rare. The low clinical suspicion and difficulty in obtaining a definitive diagnosis make for a dismal prognosis. Case presentation A literature review highlighted aetiology which included gallstone erosion, carcinoma of the pancreas and duodenal diverticulum. With written consent, we present the case of a 59 year old female, brought to the hospital following an episode of haematemesis and later found to have an AEF, secondary to metastatic retroperitoneal carcinoma - an extremely rare aetiology. Discussion There is far less literature on primary AEF when compared to secondary AEF. Furthermore, there is a variation in aetiology. Identifying the presence of a ‘herald' bleed appears to be significant. Conclusion Aorto-enteric fistulae must always be considered as a potential diagnosis in the setting of an acute upper GI haemorrhage with no apparent cause. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate a stronger correlation and agreement of yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization.Materials and Methods: Hepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors. Treatment volumes were calculated from manually drawn volumes of interest (VOI) with three-dimensional surface renderings. Radioembolization was performed with glass 90Y microspheres. PET/CT imaging was completed with scatter and attenuation correction. Three-dimensional ellipsoid VOI were drawn to encompass tumors on fused images. Tumors and livers were then explanted for inductively coupled plasma (ICP)-optical emission spectroscopy (OES) analysis of microsphere content. 90Y PET/CT and SM measurements were compared with reference standard ICP-OES measurements of tumor dosing with Pearson correlation and Bland-Altman analyses for agreement testing with and without adjustment for tumor necrosis.Results: The median infused activity was 33.3 MBq (range, 5.9-152.9). Tumor dose was significantly correlated with 90Y PET/CT measurements (r = 0.903, P < .001) and SM estimates (r = 0.607, P < .001). Bland-Altman analyses showed that the SM tended to underestimate the tumor dosing by a mean of -8.5 Gy (CI, -26.3-9.3), and the degree of underestimation increased to a mean of -18.3 Gy (CI, -38.5-1.9) after the adjustment for tumor necrosis.Conclusions: 90Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates. [ABSTRACT FROM AUTHOR]

Background & Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child–Pugh A) or cTACE (n = 21; 71% Child–Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan–Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027–0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) ( P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3–not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4–32.5) ( P = .99). Conclusions In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930 . [ABSTRACT FROM AUTHOR]

Purpose To determine, in an open-label, retrospective report, the safety and effectiveness of locoregional therapy with yttrium-90 ( 90 Y) radioembolization for patients with progressing breast cancer liver metastases (BCLMs) despite multi-agent chemotherapy. Materials and Methods Seventy-five patients with progressing BCLMs and stable extrahepatic disease were treated with radioembolization at a single institution. Retrospective review of a prospectively collected database was performed to evaluate clinical and biochemical toxicities, tumor response, overall survival (OS), and time to progression. Radiologic response assessments included Response Evaluation Criteria In Solid Tumors in primary index lesions and metabolic activity on positron emission tomography (PET). Univariate and multivariate analyses were performed. Results The mortality rate at 30 days was 4% (n = 3). Clinical toxicity and hyperbilirubinemia of grade 3 or worse occurred in 7.6% (n = 5) and 5.9% of patients (n = 4), respectively. Partial response (PR) was seen in 35.3% of patients (n = 24), stable disease (SD) in 63.2% (n = 43), and progressive disease in 1.5% (n = 1). PET imaging was available in 25 patients, and 21 (84%) had a complete response, PR, or SD. The median OS was 6.6 months (95% confidence interval [CI], 5.0–9.2 mo). The hazard ratio (HR) for OS on multivariate analysis was 0.39 (95% CI, 0.23–0.66) for tumor burden less than 25% compared with greater burden. Elevated bilirubin levels were shown to reduce OS. The HR for hepatic progression was 0.22 (95% CI, 0.05–0.98) for solitary versus multifocal disease. Conclusions Locoregional therapy with 90 Y radioembolization is safe and stops or delays the progression of targeted chemorefractory BCLMs. Adverse prognosticators were identified. [ABSTRACT FROM AUTHOR]