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Transjugular intrahepatic portosystemic shunt (TIPS) is well established as a salvage therapy for refractory esophageal variceal hemorrhage (EVH). A more controversial issue is the upper limit of Model for End-Stage Liver Disease (MELD) scores at which this procedure can be performed safely. We present 2 cases of TIPS performed for EVH in patients with severely high MELD scores as a successful intervention for hemostatic and hemodynamic stabilization, and as a bridge to urgent liver transplantation. Both patients had endoscopically confirmed EVH with high blood product transfusion and vasopressor needs despite standard medical therapy. Each received narrow bore TIPS at MELD 42 and 44, respectively, with subsequent resolution of hemorrhage despite worsening synthetic liver function. Detrimental consequences of metabolic acidosis associated with minimal residual hepatic function were avoided via continuous renal replacement therapy and mechanical ventilation, with a goal to maintain cardiopulmonary stability and favorable acid base balance. Liver transplant followed TIPS 4 and 3 days, respectively, with both patients maintaining good functional status at discharge. Both cases suggest that in patients deemed otherwise appropriate for liver transplantation, a severely high MELD score alone should not preclude TIPS as salvage therapy for refractory EVH bleeds.

To evaluate the efficacy and safety of Y90 radiation segmentectomy (RS) vs. percutaneous microwave ablation (MWA) in patients with solitary HCC ≤ 4 cm. From 2014 to 2017, 68 consecutive treatment naive patients were included (34 per treatment arm). Chi-square and t-test were used to evaluate differences in baseline demographics between groups. Objective response was evaluated using mRECIST and toxicity using CTCAE. Overall survival (OS) and progression free survival (PFS) in the targeted tumor and the remainder of liver from initial treatment was calculated using Kaplan–Meier estimation. Propensity score matching was then performed with n = 24 patients matched in each group. Similar outcome analysis was then pre-formed. In the overall study population, both groups had similar baseline characteristics with the exception of larger lesions in the RS group. There was no difference in toxicity, objective tumor response, OS and non-target liver PFS between the MWA and RS group (p’s > 0.05). In the matched cohort, the objective tumor response was 82.6% in MWA vs. 90.9%% in RS (p = 0.548). The mean OS in the MWA group (44.3 months) vs RS (59.0 months; p = 0.203). The targeted tumor mean PFS for the MWA groups was 38.6 months vs. 57.8 months in RS group (p = 0.005). There was no difference overall PFS and toxicity between the 2 matched groups. Our data suggest Y90 RS achieves similar tumor response and OS with a similar safety compared to MWA in the management of HCC lesions ≤ 4 cm. Additionally, targeted tumor PFS appears to be prolonged in the RS group with similar non-target liver PFS between RS and MWA group.

Purpose To determine predictors of survival after transarterial radioembolization of hepatic metastases from breast cancer. Materials and Methods Twenty-four patients with chemotherapy-refractory hepatic metastases from breast cancer who underwent radioembolization from 2013 to 2018 were evaluated based on various demographic and clinical factors before and after treatment. Overall survival (OS) was estimated by Kaplan–Meier method. Log-rank analysis was performed to determine predictors of prolonged OS from the time of first radioembolization and first hepatic metastasis diagnosis. Results Median OS times were 35.4 and 48.6 months from first radioembolization and time of hepatic metastasis diagnosis, respectively. Radioembolization within 6 months of hepatic metastasis diagnosis was a positive predictor of survival from first radioembolization, with median OS of 38.9 months vs 22.1 months for others (P = .033). Estrogen receptor (ER)–positive status predicted prolonged survival (38.6 months for ER+ vs 5.4 months for ER−; P = .005). The presence of abdominal pain predicted poor median OS: 12.8 months vs 38.6 months for others (P Conclusions In patients with metastatic breast cancer, radioembolization within 6 months of hepatic metastasis diagnosis and ER+ status appear to be positive predictors of prolonged survival. Conversely, baseline abdominal pain, baseline ascites, and treatment-related grade ≥ 2 toxicity at 3 months after treatment appear to be negative predictors of OS.

The complication profile following repeat Y-radioembolization (RE) is not well understood, and repeat RE is sometimes avoided because of concerns for RE-induced liver disease (REILD) and liver toxicity. The purpose of this study was to examine the incidence of REILD and liver toxicity following repeat Y-RE and to identify potential risk factors.A retrospective analysis of patients undergoing repeat RE to the same hepatic lobe between 2013 and 2018 was performed. Baseline factors were evaluated as predictors of liver toxicity, mortality, and REILD, which was defined as the presence symptomatic ascites or jaundice in the absence of biliary obstruction within 8 weeks following RE. Post-RE complications were graded according to the Common Terminology Criteria for Adverse Events version 5.A total of 39 patients underwent repeat RE with 14 (35.9%) experiencing Common Terminology Criteria for Adverse Events toxicity of grade 2 or greater, 3 (10.3%) grade 3, and no grade 4 or greater. A Model for End Stage Liver Disease score of 8 or greater was associated with grade 2 toxicity or greater (26.7% vs 75%; P = 0.013). Only 3 patients (7.7%) experienced REILD due to symptomatic ascites without jaundice. Greater than 2 REs were associated with a greater rate of 6-month mortality (12% vs 58.3%, P = 0.003), 12-month mortality (28% vs 75%, P = 0.007), and REILD (0% vs 21.4%, P = 0.016). Age, sex, microsphere type, cirrhosis, Child-Pugh, and Eastern Cooperative Oncology Group status were not significantly associated with complications, REILD, or survival.Repeat Y-RE appears to be well tolerated with a low rate of high-grade adverse events and REILD.

Renal cell carcinoma is a relatively common malignancy, with 60 to 70 thousand cases a year in the United States alone. Increased utilization of cross-sectional imaging has led to an increase in the number of early renal cell cancers seen by the medical establishment. In addition, certain patient populations have an increased risk of developing kidney cancers which may mandate aggressive screening protocols. This article discusses the epidemiology of renal cell cancers; discusses the current management guidelines from multiple specialty societies; discusses some of the surgical and interventional techniques used in the treatment of such lesions; and provides a review of the literature regarding treatments of early-stage renal cell cancers.

Thrombogenic superior vena cava syndrome is an uncommon, dangerous complication of long-standing central venous catheter use. The increased use of central venous catheters has resulted in more non-malignant cases of superior vena cava syndrome across all age groups. We present a 5-year-old male with superior vena cava syndrome associated with acute onset of severe upper extremity and facial swelling, dyspnea, and a right subclavian central venous catheter malfunction. The patient was ultimately treated with percutaneous stenting of the superior vena cava with balloon-expandable Palmaz stents following unsuccessful angioplasty, catheter-directed thrombolysis, and percutaneous thrombectomy. This case highlights a relatively uncommon complication in children from long-term central venous catheter access and describes an emerging, minimally-invasive therapeutic alternative that allows for preservation of age-appropriate superior vena cava luminal diameter as patients grow.

e15687 Background: Ki67 index is a predictor of survival in patients with metastatic neuroendocrine tumor (NET). The purpose of this study is to evaluate Ki67 index and other potential predictors of overall survival (OS) in patients with NET metastases to the liver treated with Y90 radioembolization. Methods: In an institutional review board-approved retrospective study, consecutive patients with NET metastases to the liver who were treated with Y90 radioembolization from 2013-2018 at a single institution were evaluated. Patients with documented Ki67 index were stratified according to 2017 World Health Organization (WHO) grading based on Ki67 index (G1: < 3%, G2: 3-20%, G3: > 20%). Age, gender, and objective tumor response on post Y90 imaging were also evaluated as potential predictors of survival after Y90. Objective tumor response was evaluated at 1 and/or 3 months post Y90 with multiphase MRI utilizing Response Evaluation Criteria for Solid Tumors (RECIST). Overall survival (OS) from time of Y90 was analyzed using Kaplan-Meier estimation. Predictors of survival were evaluated using log-rank test with p < 0.05 as the statistically significant level. SPSS software v. 25 (IBM Corporation, Armonk, NY) was used for all statistical analysis. Results: A total of 77 patients were identified; 36 (47%) had a documented Ki67 index from either their primary tumor, liver metastasis, or both. Primary tumor site included pancreatic (n = 10), small bowel (n = 7), pulmonary (n = 5), gastric (n = 3), large bowel (n = 3), and renal (n = 1). A primary site was not identified in several patients (n = 7).G1 tumors comprised 31% (n = 11) of patients, while G2 and G3 tumors made up 50% (n = 18) and 19% (n = 7) of the cohort, respectively. Median overall survival (OS) of the entire cohort was 51.1 months. Median OS in patients was 63.0 months in G1 tumors, 51.1 months in G2 tumors, and 3.1 months in G3 tumors (p < 0.001). Objective response on initial MRI follow-up after Y90 radioembolization also predicted prolonged OS (51.2 months versus 17.9 months, p < 0.001). Age at time of diagnosis and gender were not predictors of survival after Y90 radioembolization. Conclusions: WHO grading based on KI67 index and objective tumor response appear to be predictors of prolonged survival in patients with metastatic NET to the liver treated with Y90 radioembolization.

e15044 Background: The aim of the study was to evaluate molecular signatures and timing of yttrium-90 (Y90) as prognostic factors of survival following Y90 radioembolization (RE) in patients with chemorefractory colorectal liver metastases (CRLM). Methods: In a retrospective single-institution study, patients with unresectable, chemorefractory CRLM who had undergone genomic analysis prior to Y90 RE from 2013 to 2018 were identified. Timing of Y90 (following failure of first line vs following multiple lines of chemotherapy) and oncogenic mutation status (MAPK and PI3K pathways) were evaluated as predictors of survival length following Y-90. Survival was measured from first Y90 using Kaplan-Meier estimation and predictors of outcome were identified using log-rank analysis. Results: Overall, 58 patients with chemorefractory CRLM who underwent genomic analysis prior to Y-90 were identified. Of these, 26 (44.8%) had MAPK mutations, and 2 (3.5%) had PI3K mutations. Median survival after first Y-90 RE was 12.9 months. There was significantly prolonged overall survival (OS) in patients receiving Y90 immediately following failure of the first line of chemotherapy (FOLFOX ± bevacizumab) versus patients who underwent multiple lines of chemotherapy prior to Y90 (median OS of 16.9 vs 11.4 months for others; p = 0.023). When stratifying the cohort based on the timing of Y90, patients with WT-MAPK (n = 8) had prolonged OS if they underwent Y-90 following failure of the first line of chemotherapy (median OS of 22.3 vs 12.9 mo; p = 0.019). Patients with WT-PI3K (n = 19) had prolonged OS if they underwent Y90 following failure of the first line of chemotherapy (median OS of 16.9 vs 12 mo; p = 0.037). When analyzing the entire cohort non-stratified by timing of Y90, genetic mutation was not found to be a predictor of prolonged OS. Conclusions: Y90 RE after failure of first line of chemotherapy in CRLM appears to confer prolonged survival specifically for WT-MAPK and WT-PI3K oncogenes. Conversely, the prognosis of more favorable genetic status appears to be negated if Y90 RE is performed after failure of second or third line chemotherapies.

Lead (Pb) and cadmium (Cd) are heavy metal toxins that cause many pathophysiologic effects, including anemia. Previous in vitro studies have shown that these metals are able to replace coordinated Zinc (Zn) atoms in the Zn fingers of transcription factors and that this can alter the structure and DNA-binding characteristics of these proteins. This has lead to the hypothesis that one mechanism underlying the toxic effects of Pb and Cd is their ability to alter Zn finger transcription factor function resulting in aberrant target gene expression. A recent report that Pb is able to replace Zn in the Zn fingers of the hematopoietic transcription factor GATA-1 prompted us to address this hypothesis in the setting of MEL cell differentiation. If Pb or Cd is able to inhibit GATA-1 function, this should be detectable through alterations in chemically induced erythroid differentiation and GATA-1-dependent gene expression. Despite a strong rationale for this hypothesis, we have found no significant change in MEL differentiation, the expression of several GATA-1 target genes, or of in vitro and in vivo GATA-1 binding to DNA at concentrations well above those associated with toxic effects in humans. These results argue against the hypothesis that Pb or Cd significantly alters GATA-1 function in vivo.

Lead (Pb) and Cadmium (Cd) are among the most toxic of industrial pollutants. Anemia is one of the pathologic effects caused by exposure to these heavy metals. While previous investigations have identified the inhibition of heme synthetic enzymes by Pb and the inhibition of erythropoietin production by Cd as likely causes for these toxin-induced anemias, we were intrigued by recent reports that heavy metals, including Pb and Cd are able to replace coordinating zinc (Zn) atoms in Zn finger transcription factors (e.g., P53, TFIIIA and Sp1), disrupting their function. These reports lead us to consider the hypothesis that another cause of the anemias associated with Pb and Cd poisoning might be the displacement of Zn atoms from the two Zn fingers of the erythroid-specific transcription factor GATA-1. GATA-1 is required for normal erythropoiesis and binding sites for GATA-1 are found in the regulatory elements of erythroid-specific genes. While most of the previous studies had been performed in cell-free systems, addressing our hypothesis in a cell-based system, could add weight to pathophysiologic relevance of Zn replacement by heavy metals. To test our hypothesis, we used the model of murine erythroleukemia (MEL) cell differentiation in response to dimethylsulfoxide (DMSO). We first treated MEL cells with increasing concentrations of Pb acetate (0, 0.1, 1, 4 10 and 100 uM) or Cd acetate at the same concentrations and then measured cell viability by trypan blue staining. Decreased cell viability was seen with Pb concentrations above 4 uM by 4 days in culture. Decreased viability was not seen at any Cd concentration through 7 days. We next examined the effect of the same concentrations of Pb and Cd on differentiation of MEL cells as measured by benzidine staining. Control cells treated only with DMSO showed 0% positive staining on day 0 and 90% staining by day 7 of the experiment. Pb treatment at all concentrations had no effect on differentiation. Cd, at concentrations of 10 and 100uM, appeared to slow the kinetics of differentiation but the proportion of benzidine positive cells by day 7 was only slightly reduced. This lack of effect on our model of differentiation lead us ask whether Pb or Cd could be affecting the expression of individual genes which require GATA-1 for proper expression. We used quantitative real-time PCR to measure the levels of mRNA for β-globin, α-globin, erythropoietin receptor and GATA-1 genes daily over the 7 day course of the differentiation experiment. The β-actin gene served as a control for these experiments. As expected, levels of β- and α-globin mRNAs increased 5–10 fold during the experiment. Levels of the other genes, including β-actin, decreased over the time course. No dose-dependent changes in the levels of gene expression were observed with either Pb or Cd treatments. Given these findings, we wanted to determine whether Pb and Cd were capable of inhibiting the ability of GATA-1 to bind DNA. Following pre-incubation with the Pb or Cd, gel mobility shift experiments were conducted using MEL nuclear extract and an oligonucleotide known to bind GATA-1 from the β-globin LCR. No changes in binding were seen at the concentrations used in our experiments. Only at concentrations of 1mM or higher of either metal was DNA binding inhibited. These findings suggest that our hypothesis was incorrect and that at concentrations associated with Pb and Cd toxicity in humans there apear to be no significant effects on erythroid differentiation or GATA-1 function.