Hepatocellular Carcinoma Epigenetic Patterns Correspond to Differences in Ethnoracial Status and Treatment Response in a Single-Center Retrospective Study.

PURPOSE: To correlate epigenetic patterns with ethnoracial status and locoregional therapy (LRT) response in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DNA and RNA were extracted from 47 distinct formalin-fixed paraffin-embedded tumor samples from 42 patients with HCC (n = 14 Black, n = 19 White, n = 9 Hispanic). LRT response was determined using computed tomography (CT) or magnetic resonance (MR) imaging 3 months posttreatment of 35 tumors (n = 22 complete response, n = 13 retreatment candidates). RNA expression and DNA methylation were used to stratify patients by ethnoracial status and treatment response using partial least-squares discriminant analysis (PLS-DA). Results were validated using hierarchical clustering. Ingenuity pathway analysis was performed to identify upstream regulators and pathways. RESULTS: PLS-DA identified 100 genes and 12 methylated regions that differentiated tumors from Black from White/Hispanic patients. Hierarchical clustering clustered samples with the top 16 genes or the top 5 methylation regions. Dysregulated pathways included adrenomedullin pathway (P = .0302), EIF2 signaling (P = .00724), and several metabolic pathways. AGTR1 (log2fold = 1.59) and GSTM3 (log2fold = 2.53) represented potential differentially expressed therapeutic targets. PLS-DA identified 100 genes and 150 methylation regions that differentiated between complete responders and retreatment candidates. Hierarchical clustering clustered samples with the top 30 genes or the top 13 methylation regions. Dysregulated pathways included metabolic and DNA repair-related pathways. ASAP2 (log2fold = 0.29) and RAD50 (log2fold = 0.22) represented potential differentially expressed therapeutic targets. CONCLUSIONS: Variation in gene expression and DNA methylation patterns in patients with HCC corresponded to ethnoracial status and LRT response. These initial results suggest tumor profiling has the potential to close ethnoracial disparities and improve treatment stratification.

Bilateral dual iliac screw pelvic fixation for adult spinal deformity: a case report of a superior gluteal artery pseudoaneurysm secondary to aberrant iliac screw trajectory.

PURPOSE: To present a case of a pseudoaneurysm of a branch of the left superior gluteal artery (SGA) secondary to lateral wall perforation from an iliac screw and its subsequent evaluation and management. METHODS: Case report. RESULTS: A 67-year-old female with a history of degenerative flatback and scoliosis and pathological fractures of T12 and L1 secondary to osteodisciitis underwent a single0stage L5-S1 ALIF and T9-pelvis posterior instrumented fusion with bilateral dual iliac screw fixation, revision T11-S1 decompression, and T12 and L1 irrigation and debridement and partial corpectomies. During the operation, non-pulsatile bleeding was encountered after creating an initial trajectory for the more proximal of the two left iliac screws. While the initial post-operative course was benign, the patient was readmitted for hypotension and anemia. Computed tomography of the abdomen/pelvis demonstrated a pseudoaneurysm (2.3 cm × 2.1 cm × 2.3 cm) of a branch of the left SGA. Diagnostic angiogram confirmed a pseudoaneurysm off of one of the branches of the left SGA. Endovascular embolization using multiple coils resulted in a complete cessation of blood flow in the pseudoaneurysm. At 2 years follow-up, no symptoms suggestive of recurrence of the pseudoaneurysm were reported. CONCLUSIONS: A pseudoaneurysm of a branch of the left superior gluteal artery as a result of lateral wall perforation from an aberrantly placed iliac screw during an adult spinal deformity operation involving dual screw pelvic fixation is reported. Prompt recognition, multidisciplinary collaboration, and appropriate intervention were key in achieving a successful outcome and preventing further morbidity.

Cost-effectiveness analysis of interventional liver-directed therapies for downstaging of HCC before liver transplant.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are the 2 most used modalities for patients with HCC while awaiting liver transplant. The purpose of this study is to perform a cost-effectiveness analysis comparing TACE and TARE for downstaging (DS) patients with HCC. A cost-effectiveness analysis was performed comparing TACE and TARE in DS HCC over a 5-year time horizon from a payer's perspective. The clinical course, including those who achieved successful DS leading to liver transplant and those who failed DS with possible disease progression, was obtained from the United Network for Organ Sharing. Costs and effectiveness were measured in US dollars and quality-adjusted life years (QALYs). Probabilistic and deterministic sensitivity analyses were performed. TARE achieved a higher effectiveness of 2.51 QALY (TACE: 2.29 QALY) at a higher cost of $172,162 (TACE: $159,706), with the incremental cost-effectiveness ratio of $55,964/QALY, making TARE the more cost-effective strategy. The difference in outcome was equivalent to 104 days (nearly 3.5 months) in compensated cirrhosis state. Probabilistic sensitivity analyses showed that TARE was more cost-effective in 91.69% of 10,000 Monte Carlo simulations. TARE was more effective if greater than 48.2% of patients who received TACE or TARE were successfully downstaged (base case: 74.6% from the pooled analysis of multiple published cohorts). TARE became more cost-effective when the cost of TACE exceeded $4,831 (base case: $12,722) or when the cost of TARE was lower than $43,542 (base case: $30,609). Subgroup analyses identified TARE to be the more cost-effective strategy if the TARE cohort required 1 fewer locoregional therapy than the TACE cohort. TARE is the more cost-effective DS strategy for patients with HCC exceeding Milan criteria compared to TACE.

Malposition of a Femoral Tunneled Dialysis Catheter through a Patent Foramen Ovale.

Patent foramen ovale (PFO) is a common congenital abnormality of high prevalence in adults. Its clinical significance is magnified in a right-to-left shunt, where paradoxical embolism can have catastrophic outcomes involving the brain, heart, mesenteric circulation, or extremities. Right-to-left shunting through a PFO is caused by increased right atrial pressure, as seen in the setting of pulmonary artery hypertension or pulmonary embolism. This case highlights the relevance of central venous catheter placement in the setting of a PFO. While the patient did not experience clinical sequelae from line placement, she was at high risk for paradoxical embolus. Recognizing the possibility of a PFO during central venous catheter placement, especially in the setting of increased right pressures, should be a consideration of all interventional radiologists.

Socioeconomic and Survival Analysis of Radioembolization in Patients with Intrahepatic Cholangiocarcinoma: A Propensity Score-Adjusted Study.

PURPOSE: To determine whether transarterial radioembolization (TARE) is associated with longer survival of patients with intrahepatic cholangiocarcinoma (ICC) and whether access to TARE is influenced by socioeconomic factors. MATERIALS AND METHODS: Retrospective review of patients with ICC in the National Cancer Database from 2004 to 2018 was performed with Cox regression analysis to identify predictors of survival. Overall survival (OS) was estimated using the Kaplan-Meier method. Socioeconomic factors were compared between 2 groups using the Wilcoxon rank-sum test and χ2 test. Propensity score-matched cohorts were created between patients with ICC who did and did not undergo TARE. RESULTS: The number of patients receiving TARE for ICC increased over time from 1 in 2004 to 210 in 2018. Patients in the TARE group were more likely to be White (87.9% vs 84.3%; P = .012) and less likely to be Hispanic/Latino (7.7% vs 11.0%; P = .009). Fewer patients who underwent TARE were uninsured (0.9% vs 2.8%; P = .012). Older age, male sex, non-White race, higher tumor grade size, and stage, earlier year of diagnosis, lack of treatment with surgery or systemic therapy, and presence of lymphatic or vascular invasion exhibited significant associations with decreased survival (P < .05 for all). Patients who underwent TARE had longer survival in both unadjusted and adjusted cohorts, with an OS of 17.5 months (vs 7.2 months in the non-TARE group) after propensity matching. CONCLUSIONS: Patients with ICC who had undergone TARE experienced significantly longer survival than that experienced by those who had not after adjusting for measurable confounders. Significant socioeconomic disparities in access to TARE remain.

Influence of progestin-only hormonal use on hepatocellular adenomas: A retrospective cohort study.

OBJECTIVES: Exogenous estrogen is associated with growth of hepatocellular adenomas (HCAs), although the influence of progestin-only agents is unknown. We therefore evaluated the association of progestin-only agents on HCA progression compared to no hormone exposure and compared to estrogen exposure in female patients. STUDY DESIGN: In this single-center, retrospective cohort study of reproductive-aged female patients (ages 16-45) with diagnosed HCAs between 2003 and 2021, we evaluated radiographic HCA growth during discrete periods of well-defined exogenous hormone exposures. RESULTS: A total of 34 patients were included. Nineteen (55.9%) had follow-up scans during periods without hormone exposure, 7 (20.6%) during estrogen exposure, and 8 (23.5%) during progestin-only exposure. Over a median follow-up of 11 months, percent change in sum of adenoma diameters from baseline to last available scan was -15.0% with progestin-only agents versus 29.4% with estrogen exposure (p = 0.04), and -7.4% with no hormonal exposure (p = 0.52 compared to progestin-only). Greater than 10% growth was observed in two individuals (25.0%) with progestin-only agent use (one patient on high-dose progestin for menorrhagia) versus five individuals (71.4%) with estrogen use (p = 0.13), and 7 (36.8%) with no exogenous hormone use (p = 0.68 vs progestin-only). CONCLUSIONS: During discrete periods of progestin-only use, HCA growth overall declined, similar to declining growth during periods without exogenous hormonal exposure. This differed from discrete periods of exogenous estrogen exposure, during which time HCAs demonstrated overall increased growth. Though larger studies are needed, these findings support recent guidance supporting progestin-only agents for female patients with HCAs seeking non-estrogen alternatives for contraception. IMPLICATIONS: In this small retrospective study, we observed overall decrease in HCA size during discrete periods of progestin-only contraception use, similar to that observed during periods without exogenous hormone exposure, supporting their use as a safe alternative to estrogen-containing contraceptives in this patient population.

Clinical Outcomes and Patency after Transjugular Intrahepatic Portosystemic Shunt Reduction for Overshunting Adverse Events.

PURPOSE: To assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. MATERIALS AND METHODS: This multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). RESULTS: TIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476-1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. CONCLUSIONS: Although TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model.

PURPOSE: To investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: VX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry. RESULTS: The median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 µg/mL (interquartile range [IQR], 7.42-33.5 µg/mL), and its maximal plasma concentration (Cmax) was 0.164 µg/mL (IQR, 0.0798-0.528 µg/mL). The intratumoral concentration and Cmax of doxorubicin were similar between the groups: 4.08 µg/mL (IQR, 3.18-4.79 µg/mL) and 0.677 µg/mL (IQR, 0.315-1.23 µg/mL), respectively, in the DOX-TACE group and 1.68 µg/mL (IQR, 0.795-4.08 µg/mL) and 0.298 µg/mL (IQR, 0.241-0.64 µg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups. CONCLUSIONS: The addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.

Large thrombosed portomesenteric venous aneurysm treated with pharmacomechanical thrombolysis combined with TIPS placement.

BACKGROUND: Aneurysms are rare anomalies of the portomesenteric venous system. Thrombotic complications of these lesions can lead to mesenteric venous ischemia and bowel infarction, potentially requiring surgical intervention. Herein we describe a case of mesenteric ischemia due to a large thrombosed portomesenteric aneurysm treated with endovascular techniques. CASE PRESENTATION: A 37-year-old previously healthy male who presented with abdominal pain to his local emergency department was found to have a thrombosed 12.0 × 5.1 cm portomesenteric venous aneurysm with evidence of mesenteric ischemia on CT. When conservative management with anticoagulation failed, transhepatic pharmacomechanical thrombolysis was initially performed. This was followed by TIPS placement with additional trans-TIPS thrombectomy to improve sluggish portal outflow and prevent re-thrombosis. The patient's symptoms and imaging findings of ischemia resolved after endovascular therapy. No surgical intervention was required, and the patient was discharged on enoxaparin before being transitioned to apixaban. The TIPS remained patent at 2-year follow-up, with no change in the size of the aneurysm or re-thrombosis noted. The patient's synthetic liver function was preserved with no evidence of hepatic encephalopathy during the follow-up period. CONCLUSIONS: Endovascular therapies may be used to manage thrombotic complications of portomesenteric venous aneurysms, obviating the need for surgical intervention in selected patients.

Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model.

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70-150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.

Accuracy of Disclosed Financial Relationships between Radiologists and Industry at the 2018 RSNA Annual Meeting.

Online supplemental material is available for this article. See also the editorial by Grant in this issue.

Hepatic Toxicity After Selective Chemoembolization Is Associated With Decreased Survival Among Patients With Hepatocellular Carcinoma.

OBJECTIVE. The purpose of this study was to identify risk factors for and outcomes of hepatotoxicity after selective chemoembolization of hepatocellular carcinoma. MATERIALS AND METHODS. This retrospective study included 182 patients (136 men and 46 women; median age, 63 years [interquartile range, 57-70 years]) who underwent 338 consecutive doxorubicin drug-eluting bead (DEB) chemoembolization procedures between 2011 and 2014. Outcomes were assessed until November 2019. In 97% of procedures, two or fewer segments were targeted. The Barcelona Clinic Liver Cancer (BCLC) stage was 0 or A for 77 procedures (22.8%), B for 75 (22.2%), C for 122 (36.1%), and D for 64 (18.9%). Hepatotoxicity was defined as worsened ascites or encephalopathy or as grade 3 or 4 elevations in liver function test results, creatinine levels, or the international normalized ratio within 30 days. Risk factors were assessed by univariate and multivariable generalized estimating equations. Transplant-free survival was assessed using Cox proportional hazard models. RESULTS. Hepatotoxicity was observed after 84 of 338 procedures (24.9%) performed for 70 of 182 patients (38.5%) and was irreversible for 40 procedures (11.8%). On multivariable analysis, risk factors for irreversible toxicity included Child-Pugh class C liver function (odds ratio [OR], 4.4; 95% CI, 1.0-19.0; p = .04), BCLC stage C (OR, 5.0; 95% CI, 1.6-16.0; p = .006) or D (OR, 7.4; 95% CI, 2.1-25.5; p = .002) disease, TIPS or hepatofugal portal venous flow (OR, 6.3; 95% CI, 2.3-17.0; p < .001), and a serum α-fetoprotein level of 200 ng/mL or greater (OR, 2.6; 95% CI, 1.1-6.1; p = .03). Irreversible toxicity was associated with reduced transplant-free survival among patients who were ineligible for liver transplant (hazard ratio, 2.5; standard error, 0.42; p = .03). CONCLUSION. Irreversible hepatotoxicity was common after selective chemoembolization in patients with advanced stage disease, an elevated serum α-fetoprotein level, or reduced hepatic portal venous perfusion, and it may hasten death among patients who are ineligible for liver transplant.

Intermediate to Long-Term Clinical Outcomes of Percutaneous Cryoablation for Renal Masses.

PURPOSE: The purpose of this study was to evaluate the effectiveness and adverse outcomes of percutaneous cryoablation (CA) for treatment of renal masses in a large cohort of patients. MATERIALS AND METHODS: This retrospective analysis included 299 CA procedures (297 masses in 277 patients) performed between July 2007 and May 2018 at a single institution. The mean patient age was 66.1 years (range, 30-93 years) with 65.8% being male. A total of 234 (78.8%) masses were biopsy-proven renal cell carcinoma (RCC). The mean maximal tumor diameter was 2.5 cm (range, 0.7-6.6 cm). Efficacy was assessed only for ablations of biopsy-proven RCC, whereas the evaluation of adverse events and renal function included all masses. Complications were graded according to the Society of International Radiology classification. RESULTS: Major complications occurred in 3.0% of procedures (n = 9), none of which resulted in death or permanent disability. The mean imaging follow-up period was 27.4 months (range, 1-115) for the 199 RCC patients (204 ablated tumors) with follow-up imaging available. Complete response on initial follow-up imaging at mean 4.2 months (range, 0.3-75.6) was achieved in 195 of 204 tumors (95.6%) after a single session and in 200 of 204 tumors (98.0%) after 1 or 2 sessions. Of the RCC patients achieving complete response initially, local recurrence during the follow-up period occurred in 3 of 200 tumors (1.5%). Metastatic progression occurred in 10 of 193 (5.2%) RCC patients without prior metastatic disease during follow-up. CONCLUSIONS: CA for renal masses is safe and remains efficacious through intermediate- and long-term follow-up.

Esophagopulmonary fistula causing pulmonary arterial pseudoaneurysms and massive hemoptysis.

An esophagopulmonary fistula (EPF) may occur in patients with esophageal carcinoma and result in pulmonary abscess formation. Lung abscesses may in turn cause pulmonary artery (PA) pseudoaneurysms and life-threatening hemoptysis. We report a 59-year-old man with past medical history of metastatic distal esophageal adenocarcinoma who presented with fever, cough, and massive hemoptysis. Imaging evaluation demonstrated an EPF, associated lung abscess, and PA pseudoaneurysms. The presented case illustrates that embolization of PA pseudoaneurysms to prevent bleeding, and endoscopic esophageal covered stent graft placement to divert esophageal contents from the abscess, may facilitate a favorable outcome.

Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism in the Third Trimester of Pregnancy.

A 37-year-old woman presented with chest pain and shortness of breath in the third trimester of pregnancy. Diagnostic imaging demonstrated a saddle pulmonary embolism, severe impairment of right ventricular function, and an extensive deep venous thrombus. She underwent catheter-directed thrombolysis with tissue plasminogen activator and delivered a healthy infant at term. (Level of Difficulty: Intermediate.).