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Simple Summary: TERT promoter methylation is enriched in cancers lacking TERT genetic alterations (wild-type cancers), but its functional impact on TERT transcription remains elusive. We developed a long-read bisulfite-sequencing platform to characterize the TERT promoter methylation profile at a single-molecule level. In wild-type cancer cell lines, both epialleles were hypermethylated symmetrically on the TERT distal promoter. In the core and proximal promoter, by contrast, the transcribed epialleles were significantly more hypomethylated than the silent epialleles. Decitabine-therapy reduced the core and proximal (not the distal) promoter methylation and reactivated the silent allele. We showed that TERT allele-specific expression is amenable to in vitro epigenetic manipulation in wild-type cancers. Background: TERT promoter methylation, located several hundred base pairs upstream of the transcriptional start site, is cancer specific and correlates with increased TERT mRNA expression and poorer patient outcome. Promoter methylation, however, is not mutually exclusive to TERT activating genetic alterations, as predicted for functionally redundant mechanisms. To annotate the altered patterns of TERT promoter methylation and their relationship with gene expression, we applied a Pacific Biosciences-based, long-read, bisulfite-sequencing technology and compared the differences in the methylation marks between wild-type and mutant cancers in an allele-specific manner. Results: We cataloged TERT genetic alterations (i.e., promoter point mutations or structural variations), allele-specific promoter methylation patterns, and allele-specific expression levels in a cohort of 54 cancer cell lines. In heterozygous mutant cell lines, the mutant alleles were significantly less methylated than their silent, mutation-free alleles (p < 0.05). In wild-type cell lines, by contrast, both epialleles were equally methylated to high levels at the TERT distal promoter, but differentially methylated in the proximal regions. ChIP analysis showed that epialleles with the hypomethylated proximal and core promoter were enriched in the active histone mark H3K4me2/3, whereas epialleles that were methylated in those regions were enriched in the repressive histone mark H3K27me3. Decitabine therapy induced biallelic expression in the wild-type cancer cells, whereas the mutant cell lines were unaffected. Conclusions: Long-read bisulfite sequencing analysis revealed differences in the methylation profiles and responses to demethylating agents between TERT wild-type and genetically altered cancer cell lines. The causal relation between TERT promoter methylation and gene expression remains to be established. [ABSTRACT FROM AUTHOR]

Background: The significant adverse social and economic impact of the COVID-19 pandemic has cast broader light on the importance of addressing social determinants of health (SDOH). Medicaid Managed Care Organizations (MMCOs) have increasingly taken on a leadership role in integrating medical and social services for Medicaid members. However, the experiences of MMCOs in addressing member social needs during the pandemic has not yet been examined. Aim: The purpose of this study was to describe MMCOs' experiences with addressing the social needs of Medicaid members during the COVID-19 pandemic. Methods: The study was a qualitative study using data from 28 semi-structured interviews with representatives from 14 MMCOs, including state-specific markets of eight national and regional managed care organizations. Data were analyzed using thematic analysis. Results: Four themes emerged: the impact of the pandemic, SDOH response efforts, an expanding definition of SDOH, and managed care beyond COVID-19. Specifically, participants discussed the impact of the pandemic on enrollees, communities, and healthcare delivery, and detailed their evolving efforts to address member nonmedical needs during the pandemic. They reported an increased demand for social services coupled with a significant retraction of community social service resources. To address these emerging social service gaps, participants described mounting a prompt and adaptable response that was facilitated by strong existing relationships with community partners. Conclusion: Among MMCOs, the COVID-19 pandemic has emphasized the importance of addressing member social needs, and the need for broader consideration of what constitutes SDOH from a healthcare delivery standpoint. [ABSTRACT FROM AUTHOR]

With growing recognition of the adverse health impacts of unmet social needs, Medicaid managed care organizations (MMCOs) are increasingly focusing on addressing the social needs of Medicaid enrollees as part of a holistic approach to care. Information and knowledge sharing among MMCOs pertaining to lessons learned and promising practices from their social determinants of health (SDOH) targeted efforts can help identify successful practical approaches for navigating common challenges, developing robust SDOH programming, and effectively delivering whole-person care. Using data from interviews with 28 representatives of 8 national and regional MMCOs, this qualitative study describes the perspectives of MMCO representatives on the lessons learned and emerging promising practices from addressing SDOH among their Medicaid enrollees. Participants discussed the importance of member and community-centeredness, structured programming, and delivery system realignment in the effective delivery of whole person care. Ten lessons learned and emerging promising practices are discussed. Findings from this study suggest that success in addressing the social needs of Medicaid beneficiaries may be achieved through adaptive, data-driven, member- and community-centric efforts by MMCOs, facilitated by system-level changes that formally integrate social services within health care. Lessons learned and promising practices can serve as a foundation for identifying and evaluating best practices and guidelines for effective MMCOs' SDOH-related programming. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS), a malignancy of impaired myogenic differentiation, is the most common soft tissue pediatric cancer. PAX3-FOXO1 oncofusions drive the majority of the clinically more aggressive fusion-positive rhabdomyosarcoma (FP-RMS). Recent studies have established an epigenetic basis for PAX3-FOXO1-driven oncogenic processes. However, details of PAX3-FOXO1 epigenetic mechanisms, including interactions with, and dependence on, other chromatin and transcription factors, are incompletely understood. We previously identified a novel disease-promoting epigenetic axis in RMS, involving the histone demethylase KDM3A and the ETS1 transcription factor, and demonstrated that this epigenetic axis interfaces with PAX3-FOXO1 both phenotypically and transcriptomically, including co-regulation of biological processes and genes important to FP-RMS progression. In this study, we demonstrate that KDM3A and ETS1 colocalize with PAX3-FOXO1 to enhancers of important disease-promoting genes in FP-RMS, including FGF8, IL4R, and MEST, as well as PODXL, which we define herein as a new FP-RMS-promoting gene. We show that ETS1, which is induced by both PAX3-FOXO1 and KDM3A, exists in complex with PAX3-FOXO1, and augments PAX3-FOXO1 chromatin occupancy. We further show that the PAX3-FOXO1/ETS1 complex can be disrupted by the clinically relevant small molecule inhibitor YK-4-279. YK-4-279 displaces PAX3-FOXO1 from chromatin and interferes with PAX3-FOXO1-dependent gene regulation, resulting in potent inhibition of growth and invasive properties in FP-RMS, along with downregulation of FGF8, IL4R, MEST and PODXL expression. We additionally show that, in some FP-RMS, KDM3A also increases PAX3-FOXO1 levels. Together, our studies illuminate mechanisms of action of the KDM3A/ETS1 regulatory module, and reveal novel targetable mechanisms of PAX3-FOXO1 chromatin complex regulation, in FP-RMS., (© 2024. The Author(s).)

Purpose: The COVID-19 pandemic highlighted the importance of having emergency and acute care services close to home and emerged as an opportunity for hospital-community engagement. This study examined whether rural residents' satisfaction with their local hospital's pandemic response was associated with improved community perception of the hospital and an intention to use it in the future., Methods: Data for the study were obtained from a survey of rural residents of 6 Georgia rural communities and analyzed using multivariable logistic regression and mediation analyses., Results: Rural residents' satisfaction with their local hospital's pandemic response was associated with an improved perception of the hospital. Improvement in the perception of rural hospitals following the pandemic was found to partially mediate a positive association between community residents' satisfaction with hospital pandemic response and the intention to use the hospital when needed., Conclusion: The COVID-response efforts may have given rural hospitals an opportunity to influence public perception., (© 2023 National Rural Health Association.)

Existing work on states' efforts to address the social needs of Medicaid enrollees indicate the implementation of several state-level strategies to move Medicaid Managed Care Organizations (MMCOs) toward the provision of whole-person care. However, less is known about how these expectations drive MMCOs' SDOH efforts. To address this gap, we interviewed representatives of eight MMCOs ( N =28) and 12 state Medicaid offices ( N =17). Participants described varying state-implemented instruments for encouraging an SDOH-focus among MMCOs, including both coercive (e.g., contractual mandates) and subtle approaches (e.g., request for proposal process and performance measurement expectations). However, regardless of states' expectations, MMCOs, driven by organizational and industry-related factors, recognized the importance of addressing SDOH as part of a holistic approach to health care. Collectively, regulatory pressures, organizational strategy, and market forces influenced MMCOs' efforts to address SDOH leading to a normalization of their role in addressing members' social needs within a medical paradigm.

The androgen receptor (AR) is important in the development of both experimental and human bladder cancer. However, the role of AR in bladder cancer growth and progression is less clear, with literature indicating that more advanced stage and grade disease are associated with reduced AR expression. To determine the mechanisms underlying these relationships, we profiled AR-expressing human bladder cancer cells by AR chromatin immunoprecipitation sequencing and complementary transcriptomic approaches in response to in vitro stimulation by the synthetic androgen R1881. In vivo functional genomics consisting of pooled shRNA or pooled open reading frame libraries was employed to evaluate 97 genes that recapitulate the direction of expression associated with androgen stimulation. Interestingly, we identified CD44, the receptor for hyaluronic acid, a potent biomarker and driver of progressive disease in multiple tumor types, as significantly associated with androgen stimulation. CRISPR-based mutagenesis of androgen response elements associated with CD44 identified a novel silencer element leading to the direct transcriptional repression of CD44 expression. In human patients with bladder cancer, tumor AR and CD44 mRNA and protein expression were inversely correlated, suggesting a clinically relevant AR-CD44 axis. Collectively, our work describes a novel mechanism partly explaining the inverse relationship between AR and bladder cancer tumor progression and suggests that AR and CD44 expression may be useful for prognostication and therapeutic selection in primary bladder cancer. SIGNIFICANCE: This study describes novel AREs that suppress CD44 and an expected inverse correlation of AR-CD44 expression observed in human bladder tumors., (©2021 American Association for Cancer Research.)

Molecular alterations that confer phenotypic advantages to tumors can also expose specific therapeutic vulnerabilities. To search for potential treatments that would selectively affect metastatic cells, we examined the sensitivity of lineage-related human bladder cancer cell lines with different lung colonization abilities to chloroquine (CQ) or bafilomycin A 1 , which are inhibitors of lysosome function and autophagy. Both CQ and bafilomycin A 1 were more cytotoxic in vitro to highly metastatic cells compared with their less metastatic counterparts. Genetic inactivation of macroautophagy regulators and lysosomal proteins indicated that this was due to greater reliance on the lysosome but not upon macroautophagy. To identify the mechanism underlying these effects, we generated cells resistant to CQ in vitro. Surprisingly, selection for in vitro CQ resistance was sufficient to alter gene expression patterns such that unsupervised cluster analysis of whole-transcriptome data indicated that selection for CQ resistance alone created tumor cells that were more similar to the poorly metastatic parental cells from which the metastatic cells were derived; importantly, these tumor cells also had diminished metastatic ability in vivo. These effects were mediated in part by differential expression of the transcriptional regulator ID4 (inhibitor of DNA binding 4); depletion of ID4 both promoted in vitro CQ sensitivity and restored lung colonization and metastasis of CQ-resistant cells. These data demonstrate that selection for metastasis ability confers selective vulnerability to lysosomal inhibitors and identify ID4 as a potential biomarker for the use of lysosomal inhibitors to reduce metastasis in patients., Competing Interests: The authors declare no conflict of interest.

Purpose: We demonstrated that amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) is a tumor growth suppressor and prognostic marker in human bladder cancer. Here we determine how AGL loss enhances tumor growth, hoping to find therapeutically tractable targets/pathways that could be used in patients with low AGL-expressing tumors., Experimental Design: We transcriptionally profiled bladder cell lines with different AGL expression. By focusing on transcripts overexpressed as a function of low AGL and associated with adverse clinicopathologic variables in human bladder tumors, we sought to increase the chances of discovering novel therapeutic opportunities., Results: One such transcript was hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis. HAS2 expression was inversely proportional to that of AGL in bladder cancer cells and immortalized and normal urothelium. HAS2-driven HA synthesis was enhanced in bladder cancer cells with low AGL, and this drove anchorage-dependent and independent growth. siRNA-mediated depletion of HAS2 or inhibition of HA synthesis by 4-methylumbelliferone (4MU) abrogated in vitro and xenograft growth of bladder cancer cells with low AGL. AGL and HAS2 mRNA expression in human tumors was inversely correlated in patient datasets. Patients with high HAS2 and low AGL tumor mRNA expression had poor survival, lending clinical support to xenograft findings that HAS2 drives growth of tumors with low AGL., Conclusions: Our study establishes HAS2-mediated HA synthesis as a driver of growth of bladder cancer with low AGL and provides preclinical rationale for personalized targeting of HAS2/HA signaling in patients with low AGL-expressing tumors., (©2015 American Association for Cancer Research.)

Objective: The purpose of this study was to assess the efficacy and safety of flow-directed catheter thrombolysis for treatment of submassive pulmonary embolism (PE)., Materials and Methods: In this single-institution retrospective study, 19 patients (nine men and 10 women; mean age [± SD], 54 ± 13 years) with submassive PE underwent catheter-directed thrombolysis between 2009 and 2013. Presenting symptoms included dyspnea in 18 of 19 (95%) cases. Submassive PE was diagnosed by pulmonary CT arteriography and right ventricular strain. PE was bilateral in 17 of 19 (89%) and unilateral in two of 19 (11%) cases. Thrombolysis was performed via a pulmonary artery (PA) catheter infusing 0.5- 1.0 mg alteplase per hour and was continued to complete or near complete clot dissolution with reduction in PA pressure. IV systemic heparin was administered. Measured outcomes included procedural success, PA pressure reduction, clinical success, survival, and adverse events., Results: Procedural success, defined as successful PA catheter placement, fibrinolytic agent delivery, PA pressure reduction, and achievement of complete or near complete clot dissolution, was achieved in 18 of 19 (95%) cases. Thrombolysis required 57 ± 31 mg of alteplase administered over 89 ± 32 hours. Initial and final PA pressures were 30 ± 10 mm Hg and 20 ± 8 mm Hg (p < 0.001). All 18 (100%) technically successful cases achieved clinical success because all patients experienced symptomatic improvement. Eighteen of 19 (95%) patients survived to hospital discharge; 18 of 19 (95%) and 15 of 16 (94%) patients had documented 1-month and 3-month survival. One fatal case of intracranial hemorrhage was attributed to supratherapeutic anticoagulation because normal fibrinogen levels did not suggest remote fibrinolysis; procedural success was not achieved in this case because of early thrombolysis termination. No other complications were encountered., Conclusion: Among a small patient cohort, flow-directed catheter thrombolysis with alteplase effectively dissolved submassive PE and reduced PA pressure. Postprocedure short-term survival was high, and patients undergoing thrombolysis required close observation for bleeding events.

Background: Bladder cancer is the most common malignancy of the urinary system, yet our molecular understanding of this disease is incomplete, hampering therapeutic advances., Methods: Here we used a genome-wide functional short-hairpin RNA (shRNA) screen to identify suppressors of in vivo bladder tumor xenograft growth (n = 50) using bladder cancer UMUC3 cells. Next-generation sequencing was used to identify the most frequently occurring shRNAs in tumors. Genes so identified were studied in 561 patients with bladder cancer for their association with stratification of clinical outcome by Kaplan-Meier analysis. The best prognostic marker was studied to determine its mechanism in tumor suppression using anchorage-dependent and -independent growth, xenograft (n = 20), and metabolomic assays. Statistical significance was determined using two-sided Student t test and repeated-measures statistical analysis., Results: We identified the glycogen debranching enzyme AGL as a prognostic indicator of patient survival (P = .04) and as a novel regulator of bladder cancer anchorage-dependent (P < .001), anchorage-independent (mean ± standard deviation, 180 ± 23.1 colonies vs 20±9.5 in control, P < .001), and xenograft growth (P < .001). Rescue experiments using catalytically dead AGL variants revealed that this effect is independent of AGL enzymatic functions. We demonstrated that reduced AGL enhances tumor growth by increasing glycine synthesis through increased expression of serine hydroxymethyltransferase 2., Conclusions: Using an in vivo RNA interference screen, we discovered that AGL, a glycogen debranching enzyme, has a biologically and statistically significant role in suppressing human cancer growth., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The quantitative relationship between tumor morphology and malignant potential has not been explored in liver tumors. We designed a computer algorithm to analyze shape features of hepatocellular carcinoma (HCC) and tested feasibility of morphologic analysis., Materials and Methods: Cross-sectional images from 118 patients diagnosed with HCC between 2007 and 2010 were extracted at the widest index tumor diameter. The tumor margins were outlined, and point coordinates were input into a MATLAB (MathWorks Inc., Natick, Massachusetts, USA) algorithm. Twelve shape descriptors were calculated per tumor: the compactness, the mean radial distance (MRD), the RD standard deviation (RDSD), the RD area ratio (RDAR), the zero crossings, entropy, the mean Feret diameter (MFD), the Feret ratio, the convex hull area (CHA) and perimeter (CHP) ratios, the elliptic compactness (EC), and the elliptic irregularity (EI). The parameters were correlated with the levels of alpha-fetoprotein (AFP) as an indicator of tumor aggressiveness., Results: The quantitative morphometric analysis was technically successful in all cases. The mean parameters were as follows: compactness 0.88±0.086, MRD 0.83±0.056, RDSD 0.087±0.037, RDAR 0.045±0.023, zero crossings 6±2.2, entropy 1.43±0.16, MFD 4.40±3.14 cm, Feret ratio 0.78±0.089, CHA 0.98±0.027, CHP 0.98±0.030, EC 0.95±0.043, and EI 0.95±0.023. MFD and RDAR provided the widest value range for the best shape discrimination. The larger tumors were less compact, more concave, and less ellipsoid than the smaller tumors (P < 0.0001). AFP-producing tumors displayed greater morphologic irregularity based on several parameters, including compactness, MRD, RDSD, RDAR, entropy, and EI (P < 0.05 for all)., Conclusion: Computerized HCC image analysis using shape descriptors is technically feasible. Aggressively growing tumors have wider diameters and more irregular margins. Future studies will determine further clinical applications for this morphologic analysis.

Purpose: We aimed to assess the safety, efficacy, and clinical outcomes of splenic artery embolization (SAE)., Materials and Methods: A total of 50 patients (male:female, 33:17; mean age, 49 years) who underwent 50 SAEs between 1998 and 2011 were retrospectively studied. The procedure indications included aneurysm or pseudoaneurysm (n=15), gastric variceal hemorrhage (n=15), preoperative reduction of surgical blood loss (n=9), or other (n=11). In total, 22 procedures were elective, and 28 procedures were urgent or emergent. The embolic agents included coils (n=50), gelatin sponges (n=15), and particles (n=4). The measured outcomes were the technical success of the procedure, efficacy, side effects, and the 30-day morbidity and mortality rates., Results: All embolizations were technically successful. The procedure efficacy was 90%; five patients (10%) had a recurrent hemorrhage requiring a secondary intervention. Side effects included hydrothorax (n=26, 52%), thrombocytosis (n=16, 32%), thrombocytopenia (n=13, 26%), and postembolization syndrome (n=11, 22%). Splenic infarcts occurred in 13 patients (26%). The overall and procedure-specific 30-day morbidity rates were 38% (19/50) and 14% (splenoportal thrombosis, 3/50; encapsulated bacterial infection, 1/50; splenic abscess, 1/50; femoral hematoma requiring surgery, 1/50; hydrothorax requiring drainage, 1/50). The overall and procedure-specific 30-day mortality rates were 8% (4/50) and 0%. The multivariate analysis showed that advanced patient age (P = 0.037), postprocedure thrombocytopenia (P = 0.008), postprocedure hydrothorax (P = 0.009), and the need for a secondary intervention (P = 0.004) predicted the 30-day morbidity, while renal insufficiency (P < 0.0001), preprocedure hemodynamic instability (P = 0.044), and preprocedure leukocytosis (P < 0.0001) were prognostic factors for the 30-day mortality., Conclusion: SAE was performed with high technical success and efficacy, but the outcomes showed nontrivial morbidity rates. Elderly patients with thrombocytopenia and hydrothorax after SAE, and patients who require secondary interventions, should be monitored for complications.

Purpose: To assess the relationship between body mass index (BMI), subcutaneous and intra-abdominal fat, liver density, and histopathologic hepatic steatosis., Materials and Methods: In this retrospective study, 143 patients (male/female, 67/76; mean age, 50 years) underwent a non-targeted transjugular (n = 125) or percutaneous (n = 18) liver biopsy between 2006 and 2010. The biopsy indications included chronic liver parenchymal disease staging (n = 88), elevated enzymes (n = 39), or other reasons (n = 16). The BMI and non-contrast liver computed tomography liver density were recorded for each patient. The thicknesses of the anterior, posterior, and posterolateral subcutaneous fat, along with the intra-abdominal fat, were measured. The values were then correlated with histopathologic steatosis., Results: Of the patients, 47/143 (32%), 39/143 (28%), and 57/143 (40%) were normal weight, overweight, and obese, respectively. Steatosis was present in 13/47 (28%) of normal weight, 18/39 (46%) of overweight, and 38/57 (67%) of obese patients. Significant differences in BMI (26.7 kg/m(2) vs. 31.7 kg/ m2 vs. 35.0 kg/m(2), P < 0.001), liver density (52.8 HU vs. 54.4 HU vs. 42.0 HU, P < 0.001), anterior subcutaneous (1.8 cm vs. 2.4 cm vs. 2.9 cm, P < 0.001), posterolateral subcutaneous (2.8 cm vs. 3.2 cm vs. 4.4 cm, P < 0.004), posterior subcutaneous (1.9 cm vs. 2.5 cm vs. 3.4 cm, P < 0.001), and intra-abdominal fat thickness (1.1 cm vs. 1.3 cm vs. 1.4 cm, P < 0.013) were identified in patients with different degrees of steatosis (none, minimal to mild, moderate to severe, respectively). BMI (r = 0.37, P < 0.001) and the anterior subcutaneous fat (r = 0.30, P < 0.001) had a moderate correlation with the presence of liver steatosis. A combination of a BMI ≥ 32.0 kg/ m(2) and an anterior subcutaneous fat thickness ≥ 2.4 cm had a 40% sensitivity and 90% specificity for the identification of steatosis., Conclusion: Increase in the anthropomorphic metrics of obesity is associated with an increased frequency of liver steatosis.

Purpose: To describe the utility, safety, and efficacy of endovascular intervention for treating bleeding events after robotic pancreaticobiliary surgery., Materials and Methods: In this retrospective study, six patients (male/female, 3/3; mean age, 64 years) with histories of robotic pancreaticobiliary resection were referred for endovascular management of delayed postoperative intra-abdominal hemorrhage. Visceral angiography was performed, and the sites of suspected arterial hemorrhage were interrogated with selective microcatheter arteriography. The visualized bleeding sources were treated using catheter-directed embolotherapy with metallic coils, bare metal or covered stent insertion, or a combination of the two. The measured outcomes included the technical success of the angiographic occlusion, procedure safety, and procedure efficacy., Results: Pseudoaneurysms resulted in bleeding in six cases (100%). The endovascular interventions included coil embolization in three cases (50%), covered stent exclusion in two cases (33%), and bare metal stent-assisted coil embolization in one case (17%). The technical success was 100%, with complete cessation of bleeding in all cases. No immediate or delayed procedure-related complications were encountered in any of the patients. The efficacy of the endovascular therapy was 100% in this series, with no recurrent hemorrhage during the mean clinical follow-up period of 262 days (range, 67-446 days)., Conclusion: Endovascular therapy provides a minimally invasive, safe, and effective method for managing hemorrhagic events after complicated pancreaticobiliary surgery.

Hepatic lobar atrophy-hypertrophy complex formation is an uncommonly reported sequella of hepatic arterial embolotherapy procedures. Whereas radiation-induced hepatic lobar ablation has been described after intra-arterial therapy with yttrium-90 microspheres, this phenomenon has not been reported after transcatheter arterial chemoembolization. Here, we report a case of prominent hepatic lobar atrophy with contralateral lobar hypertrophy after chemoembolization and suggest a mechanism by which arterial embolization contributes to the volumetric response.

Uterine leiomyomas (fibroids) are the most common tumors in women of reproductive age and a cause of significant morbidity in this patient population. Depending on the fibroid location, they can be the cause of a variety of symptoms, such as abnormal uterine bleeding, constipation, urinary frequency, and pain. Historically, hysterectomy has been the primary treatment option, and uterine fibroids remain the leading cause for hysterectomy in the United States. However, women who do not wish to undergo hysterectomy now have a variety of less invasive options available, including uterine artery embolization. This article discusses uterine artery embolization as well as some of the other treatment strategies for symptomatic uterine fibroids. In many situations, there may be no single best treatment option but several viable alternatives. Each option is discussed with consideration of outcomes, complications, and, when possible, cost-effectiveness. The recommendations in this article are the result of evidence-based consensus of the ACR Appropriateness Criteria® Expert Panel on Interventional Radiology., (Copyright © 2011. Published by Elsevier Inc.)

Objective: The goal of this article is to describe potential technical complications related to transjugular intrahepatic portosystemic shunts (TIPS) placement and to discuss strategies to avoid and manage complications if they arise., Conclusion: TIPS is an established interventional therapy for complications of portal hypertension. Although TIPS remains a relatively safe procedure, direct procedure-related morbidity rates are as high as 20%. The technical complexity of this intervention increases the risk for methodologic mishaps during all phases of TIPS placement, including venous access and imaging, transhepatic needle puncture, shunt insertion, and variceal embolization. Thus, interventional radiologists require a thorough stepwise understanding of TIPS insertion, possible adverse sequela, and technical tips and tricks to maximize the safety of this procedure.

Yttrium-90 (Y-90) radioembolization, also known as selective internal radiation therapy (SIRT), is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT, Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor, leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT, the specific indications for this therapy have yet to be defined. Typically, SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However, it has also found increasing use as a salvage therapy in chemo-refractory patients. Herein, the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive, chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.