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Nicholas Fidelman,1 Curt Johanson,1 Maureen P Kohi,1 K Pallav Kolli,1 Ryan M Kohlbrenner,1 Evan D Lehrman,1 Andrew G Taylor,1 R Kate Kelley,2 Francis Y Yao,3 John P Roberts,4 Robert K Kerlan11Department of Radiology and Biomedical Imaging; 2Department of Medicine – Division of Gastrointestinal Oncology; 3Department of Medicine – Division of Hepatology; 4Department of Surgery – Division of Transplant Surgery, University of California San Francisco, San Francisco, CA, USAPurpose: To determine whether chemoembolization using drug-eluting beads (DEB-TACE) is safe and effective for liver transplantation candidates with liver-limited hepatocellular carcinoma (HCC) without vascular invasion and baseline hepatic dysfunction.Materials and methods: Seventeen adult liver transplantation candidates (median age 66 years, range 58–73 years; 13 men) with HCC were treated with DEB-TACE as a part of Stage 1 of a prospective single-institution Phase II trial. All patients had marginal hepatic reserve based on at least one of the following criteria: ascites (n=14), bilirubin between 3 and 6 mg/dL (n=5), AST 5–10 times upper normal limit (n=1), INR between 1.6 and 2.5 (n=4), portal vein thrombosis (n=2), and/or portosystemic shunt (n=2). Primary study objectives were safety and best observed radiographic response.Results: Thirty-seven DEB-TACE procedures were performed. Objective response rate and disease control rate were 63% and 88%, respectively. HCC progression was observed in 12 patients. Median time to progression was 5.6 months (range 0.9–13.6 months). Within 1 month following DEB-TACE, 13 patients (76%) developed grade 3 or 4 AE attributable to the procedure. Four patients (all within Milan Criteria) were transplanted (2.7–6.9 months after DEB-TACE), and 12 patients died (1.8–32 months after DEB-TACE). All deaths were due to liver failure that was either unrelated to HCC (n=5), in the setting of metastatic HCC (n=5), or in the setting of locally advanced HCC (n=2). Mortality rate at 1 month was 0%.Conclusions: DEB-TACE achieves tumor responses but carries a high risk of hepatotoxicity for liver transplant candidates with HCC and marginal hepatic reserve.Keywords: hepatocellular carcinoma, chemoembolization, liver transplantation

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research., Competing Interests: Conflict of interest: Y.C.G. Lee receives drainage kits without charge for participants of a clinical trial he leads. J.S. Reisenauer has a research grant with Intuitive Surgical and is an educational consultant for Vergent, Isola, Medview and Imvaria, outside the submitted work. M.M. DeCamp is an educational consultant for PulmonX and is on the scientific advisory board for Pleural Dynamics. D.J. Feller-Kopman is an educational consultant for AstraZeneca, Noah Medical and Boston Scientific, outside the submitted work. H. Grosu has a sponsored research agreement with Known Medicine. J.F.B. Chick is an educational consultant and speaker for Inari Medical, Guerbet, C. R. Bard, Argon Medical Devices, Boston Scientific, NXT Biomedical and AiDoc, outside the submitted work. F. Maldonado received research funding from Medtronic and personal consulting fees from J&J and Intuitive, outside of the submitted work. The remaining authors do not have any disclosures or conflicts of interest to report., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear., Aims: In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS., Methods: Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year. We developed multivariable logistic regression models to identify clinical/procedural characteristics associated with rebleeding., Results: We identified 476 patients, predominately middle-aged (mean age 57), male (62%) and White (65%), with mean MELD-Na 16. 16% (n = 77) had a rebleeding event; these patients were more likely to be male (p = 0.016), with higher serum creatinine (p = 0.005), MELD-Na (p = 0.0002), portal hypertensive gastropathy on pre-TIPSS upper endoscopy (p = 0.000) and with higher incidence of TIPSS revision (p = 0.000). There were no significant differences in type of TIPSS endoprosthesis, concurrent embolotherapy, and post-TIPSS pressure gradients between those who experienced rebleeding and those who did not. After adjusting for TIPSS revision, multivariable analysis revealed MELD-Na and presence of portal hypertensive gastropathy on pre-TIPSS endoscopy were independently associated with rebleeding., Conclusions: In this retrospective analysis of a multicentre, nationally representative database, we found that apart from TIPSS-related factors, high MELD-Na and portal hypertensive gastropathy on pre-TIPSS endoscopy were independent predictors of rebleeding within 1 year following TIPSS. These variables may be used to identify high-risk patients who may require additional monitoring following TIPSS., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: While transjugular intrahepatic portosystemic shunt (TIPS) is traditionally considered a bridge to liver transplant (LT), some patients achieve long-term transplant-free survival (TFS) with TIPS alone. Prognosis and need for LT should not only be assessed at time of procedure, but also re-evaluated in patients with favorable early outcomes., Approach and Results: Adult TIPS recipients in the multicenter Advancing Liver Therapeutic Approaches retrospective cohort study were included (N=1,127 patients; 2,040 person-years follow-up). Adjusted competing risk regressions were used to assess factors associated with long-term post-TIPS clinical outcomes at time of procedure and at 6 months post-TIPS. MELD-Na at TIPS was significantly associated with post-TIPS mortality (sHR of death 1.1 [p=0.42], 1.3 [p=0.04], and 1.7 [p<0.01] for MELD-Na 15-19, 20-24, and ≥25 relative to MELD-Na <15, respectively). MELD 3.0 was also associated with post-TIPS outcomes. Among the 694 (62%) patients who achieved early (6 mo) post-TIPS TFS, rates of long-term TFS were 88% at 1-year and 57% at 3-years post-TIPS. Additionally, a within-individual increase in MELD-Na score of >3 points from TIPS to 6 months post-TIPS was significantly associated with long-term mortality, regardless of initial MELD-Na score (sHR of death 1.8, p<0.01). For patients with long-term post-TIPS TFS, rates of complications of the TIPS or portal hypertension were low., Conclusions: Among patients with early post-TIPS TFS, prognosis and need for LT should be reassessed, informed by post-procedure changes in MELD-Na and clinical status. For selected patients, "destination TIPS" without LT may offer long-term survival with freedom from portal hypertensive complications., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: To state the position of the Society of Interventional Radiology (SIR) on the endovascular management of chronic iliofemoral venous obstruction with metallic stents., Materials and Methods: A multidisciplinary writing group with expertise in treating venous disease was convened by SIR. A comprehensive literature search was conducted to identify studies on the topic of interest. Recommendations were drafted and graded according to the updated SIR evidence grading system. A modified Delphi technique was used to achieve consensus agreement on the recommendation statements., Results: A total of 41 studies, including randomized trials, systematic reviews and meta-analyses, prospective single-arm studies, and retrospective studies were identified. The expert writing group developed 15 recommendations on the use of endovascular stent placement., Conclusions: SIR considers the use of endovascular stent placement for chronic iliofemoral venous obstruction to be likely to help selected patients, but the risks and benefits have not been fully quantified in well-designed randomized studies. SIR recommends urgent completion of such studies. In the meantime, careful patient selection and optimization of conservative therapy are recommended prior to stent placement, with attention to appropriate stent sizing and quality procedural technique. The use of multiplanar venography with intravascular ultrasound is suggested in diagnosing and characterizing obstructive iliac vein lesions and in guiding stent therapy. After stent placement, SIR recommends close patient follow-up to ensure optimal antithrombotic therapy, durable symptom response, and early identification of adverse events., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation., Materials and Methods: Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×10 9 /L., Results: A total of 601 patients were included. The median absolute change in platelets was 1 × 10 9 /L (-26 × 10 9 /L to 25 × 10 9 /L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 10 9 /L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10-1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 10 9 /L before TIPS. The median absolute platelet change was 14 × 10 9 /L (2 × 10 9 /L to 34 × 10 9 /L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup., Conclusions: TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 10 9 /L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 10 9 /L., (Copyright © 2023. Published by Elsevier Inc.)

Background: To date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation., Methods: Patients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy., Primary Endpoint: objective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated., Results: Part A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2-33.9%), median PFS 1.8 months (95% CI, 1.7-21.4), median OS 7.8 months (95% CI, 3.1-not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0-22.8%), median PFS 2.0 months (95% CI, 1.9-3.4), median OS 4.8 months (95% CI, 4.1-8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours., Discussion: Treatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs., Clinical Trial Registration: ClinicalTrials.gov NCT03136055., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database., Approach and Results: Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes.Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p =0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets., Conclusions: Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Purpose: We sought to identify which aspects of the referring clinician experience are most strongly correlated with overall satisfaction, and hence of greatest relevant importance to referring clinicians., Methods: A survey instrument assessing referring clinician satisfaction throughout 11 domains of the radiology process map was distributed 2720 clinicians. The survey contained sections assessing each process map domain, with each section including a question about satisfaction overall in that domain and multiple more granular questions. The final question on the survey was overall satisfaction with the department. Univariate logistic regression and multivariate logistic regression were performed to assess the association between individual survey questions and overall satisfaction with the department., Results: 729 referring clinicians (27%) completed the survey. Using univariate logistic regression nearly every question was associated with overall satisfaction. Amongst the 11 domains of the radiology process map multivariate logistic regression identified the following as mostly strongly associated with overall satisfaction: results/reporting overall (odds ratio 4.71; 95% confidence interval 2.15-10.23), section with which work most closely overall (3.39; 1.28-8.64), and inpatient radiology overall (2.39; 1.08-5.08). Other survey questions associated with overall satisfaction on multivariate logistic regression were attending radiologist interactions (odds ratio 3.71; 95% confidence interval 1.54-8.69), timeliness of inpatient radiology results (2.91; 1.01-8.09), technologist interactions (2.15; 0.99-4.40), appointment availability for urgent outpatient studies (2.01; 1.08-3.64), and guidance for selecting correct imaging study (1.88; 1.04-3.34)., Conclusion: Referring clinicians value most the accuracy of the radiology report and their interactions with attending radiologists, particularly within the section they work most closely., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To establish the updated position of the Society of Interventional Radiology (SIR) on the endovascular management of acute iliofemoral deep vein thrombosis (DVT)., Materials and Methods: A multidisciplinary writing group with expertise in treating venous diseases was convened by SIR. A comprehensive literature search was conducted to identify studies on the topic of interest. Recommendations were drafted and graded according to the updated SIR evidence grading system. A modified Delphi technique was used to achieve consensus agreement on the recommendation statements., Results: A total of 84 studies, including randomized trials, systematic reviews and meta-analyses, prospective single-arm studies, and retrospective studies were identified and included in the review. The expert writing group developed 17 recommendations that pertain to the care of patients with acute iliofemoral DVT with the use of endovascular venous interventions., Conclusions: SIR considers endovascular thrombus removal to be an acceptable treatment option in selected patients with acute iliofemoral DVT. Careful individualized risk assessment, high-quality general DVT care, and close monitoring during and after procedures should be provided., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications., Methods: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT)., Results: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13)., Discussion: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS., (Copyright © 2021 by The American College of Gastroenterology.)

Background: To evaluate the efficacy of percutaneous and endoscopic therapeutic interventions for biliary strictures and leaks following LT in children., Methods: Retrospective analysis of 49 consecutive pediatric liver transplant recipients (27 girls, 22 boys, mean age at transplant 3.9 years) treated at our institution from 1989 to 2019 for biliary leak and/or biliary stricture was performed. Minimally invasive approach was considered clinically successful if it resulted in patency of the narrowed biliary segment and/or correction of the biliary leak., Results: Forty-two patients had a stricture at the biliary anastomosis; seven had a biliary leak. After an average 13.8 years of follow-up, long-term clinical success with minimally invasive treatment (no surgery or re-transplant) was achieved for 24 children (57%) with biliary stricture and 4 (57%) with biliary leaks. Eight patients required re-transplant; however, only one was due to failure of both percutaneous and surgical management. For biliary strictures, failure of non-surgical management was associated with younger age at stricture diagnosis (p < .02)., Conclusions: Percutaneous and endoscopic management of biliary strictures and leaks after LT in children is associated with a durable result in >50% of children., (© 2021 Wiley Periodicals LLC.)

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m 2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Purpose: To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach., Methods: Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands., Results: A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5-2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia., Conclusions: PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study.

Seriously ill surgical patients require complex and integrated surgical, interventional, and medical management to balance the risks and benefits that complicate decision-making. Palliative care principles can aid surgeons in these cases. To illustrate this, we describe a scenario of a patient with unresectable hepatocellular carcinoma with portal vein tumor thrombus causing portal hypertension. We discuss options for managing the sequelae of portal hypertension, including varices and ascites. We explore the interventional and surgical options for mitigating or palliating the underlying portal hypertension. Advances in interventional radiological techniques can facilitate the creation of transjugular intrahepatic portosystemic shunts (TIPSs), even with extensive portal vein thrombus. If interventional approaches are not possible, surgical shunts can be considered but carry significant risks that must be weighed against the benefits. To communicate effectively, we outline key steps to breaking bad news. To make shared decisions in challenging cases, we describe how to elicit a patient's hopes, expectations, concerns, and preferences; how to synthesize goals of care from these stated values; and how to use those goals to guide decision-making.

Competing Interests: Conflict of Interest M.P.K. has received consulting fees from Medtronic, Boston Scientific, and Penumbra.

Intravenous (IV) contrast material is used extensively for CT and MRI scans done in emergency departments (ED). Its use is essential to make many critical diagnoses in ED patients. While adverse reactions can occur, newer research has added to our knowledge of IV contrast media tolerance and safety leading to improved and more liberal guidelines for intravenous contrast use. The updated information described in this review article indicates how intravenous contrast can be used safely in more patients, more expeditiously and with fewer precautions than with prior guidelines. This review article explains the basis for the new recommendations for intravenous contrast material use and describes indicated precautions and preparations to avoid adverse reactions for iodinated agents used for CT and gadolinium agents for MRI.

Background: This retrospective study evaluated and compared the diagnostic accuracy and suitability of tissue specimens for advanced molecular diagnostic testing obtained via 2 different techniques for percutaneous biopsy of primary and metastatic liver tumors., Patients and Methods: Samples from 137 patients with liver masses who underwent concurrent fine-needle aspiration biopsy with cell block (FNAB-CB) and core needle biopsy (CNB) at 2 hospitals were assessed for diagnostic accuracy, tumor fraction, and tumor cellularity. A subset of FNAB-CBs, that were deemed to have less or equal tumor cellularity compared with CNBs, had level sections performed and were reassessed for tumor cellularity., Results: Diagnostic accuracy was 96% for FNAB and 93% for CNB (P=.267). In FNAB-CBs, tumor fraction was significantly higher than in CNB samples (67% vs 36%; P<.0001), whereas nontumor components were significantly lower (stromal component, 7% vs 29%; P<.0001; background benign hepatocytes, 25% vs 36%; P=.003). Additionally, in 44% of cases, FNAB-CB tumor cellularity was equal to or greater than that of the concurrent CNB., Conclusions: In the current age of personalized medicine, a minimally invasive, safe approach to obtaining adequate tissue for myriad molecular testing is paramount. We have shown that FNAB sampling is diagnostically accurate and produces higher tumor fractions than CNB. Thus, FNAB should be strongly considered as an initial sampling modality, especially for patients in whom molecular tests will determine management.

Purpose: To evaluate efficacy and safety of transjugular liver biopsy (TJLB) via the left hepatic vein in patients with left lobe-only liver transplants (LLOTs)., Materials and Methods: Retrospective review revealed 43 TJLBs performed in 26 patients with LLOTs (mean age 51.3 y; range, 18-73 y) between January 2009 and June 2016 at a single institution. A comparison group of 44 randomly selected TJLBs performed in 37 orthotopic whole liver transplant (OWLT) recipients (mean age 57.6 y; range, 35-74 y) during the same time period was evaluated. Patient demographics, type and age of transplant, technical success, adequacy of samples, number of portal tracts obtained, pathologic diagnosis, and complication rate were reviewed., Results: Technical success was achieved in 98% (42/43) of LLOT procedures. TJLB failed in 1 patient with LLOT, in whom no patent hepatic veins were identified. Technical success was achieved in 100% (44/44) in the OWLT group. Mean (SD) number of needle passes was 4.12 (1.25) in the LLOT group vs 3.95 (1.28) in the OWLT group (P = .54). Mean (SD) specimen length was 1.16 (0.75) cm in the LLOT group vs 1.19 (0.58) cm in the OWLT group (P = .78). Mean (SD) number of portal tracts obtained in the LLOT group was 10.7 (5.26) vs 12.3 (4.68) in the OWLT group (P = .17). No major complications were observed in either group., Conclusions: TJLB in adult patients with LLOTs appears safe and feasible, with favorable rates of technical success and adequacy of sampling., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Anastomosing hemangiomas are a rare subtype of benign vascular hemangioma which most commonly arise in the genitourinary tract and retroperitoneum. In only a small number of reports has this entity been shown originating within the liver parenchyma. Despite their benign behavior, on contrast-enhanced computer tomography and magnetic resonance imaging studies anastomosing hemangiomas can demonstrate enhancement characteristics similar to primary and metastatic liver lesions. This case report highlights the imaging features of this entity and provides a brief review of the limited literature that exists on this rare hepatic lesion.

Purpose: To assess the effectiveness of disposable radiation-absorbing surgical drapes on operator radiation dose during transjugular liver biopsy (TJLB)., Materials and Methods: This dual-arm prospective, randomized study was conducted between May 2017 and January 2018 at a single institution. TJLB procedures (N = 62; patient age range, 19-80 y) were assigned at a 1:1 ratio to the use of radiation-absorbing surgical drapes or standard surgical draping. The primary outcome was cumulative radiation equivalent dose incident on the operator, as determined by an electronic personal dosimeter worn at the chest during each procedure. Cumulative kerma-area product (KAP), total fluoroscopy time, and total number of exposures used during each liver biopsy procedure were also determined., Results: Mean radiation dose incident on the operator decreased by 56% with the use of radiation-absorbing drapes (37 μSv ± 35; range, 4-183 μSv) compared with standard draping (84 μSv ± 58; range, 11-220 μSv). Radiation incident on the patient was similar between groups, with no significant differences in mean KAP, total fluoroscopy time, and number of exposures acquired during the procedures., Conclusions: Use of disposable radiation-absorbing drapes reduces scatter radiation to interventionalists performing TJLB., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess radiation dose reduction during uterine fibroid embolization (UFE) using an optimized angiographic processing and acquisition platform., Materials and Methods: Radiation dose data for 70 women (mean age, 46 y; range, 34-67 y) who underwent UFE were retrospectively analyzed. Twenty-one patients underwent UFE using the baseline fluoroscopic and angiographic image acquisition platform, and 49 underwent UFE after implementing an optimized imaging platform in otherwise identical angiography suites. Cumulative kerma-area product (CKAP), cumulative air kerma (CAK), total fluoroscopy time, and image exposure number were collected for each procedure. Image quality was assessed by 3 interventional radiologists blinded to the platform used for image acquisition and processing., Results: Patients undergoing UFE using the new x-ray fluoroscopy platform had significantly lower CKAP and CAK indicators than patients for whom baseline settings were used. Mean CKAP decreased by 60% from 438.5 Gy · cm 2 (range, 180.3-1,081.1 Gy · cm 2 ) to 175.2 Gy · cm 2 (range, 47.1-757.0 Gy · cm 2 ; P < .0001). Mean CAK decreased by 45% from 2,034.2 mGy (range, 699.3-5,056.0 mGy) to 1,109.8 mGy (range, 256.6-4,513.6 mGy; P = .001). No degradation of image quality was identified through qualitative evaluation., Conclusions: Significant reduction in patient radiation dose indicators can be achieved with use of an optimized image acquisition and processing platform., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Background: This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using 90 Y glass microspheres., Methods: Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of 90 Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.5 years after radioembolization. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Time to maximum response, response duration, progression-free survival (PFS) (hepatic and extrahepatic), and overall survival (OS) were measured., Results: Median target dose and activity were 109.4 Gy and 2.6 GBq per treatment session, respectively. Majority of clinical AE were grade 1 or 2 in severity. Patients with colorectal cancer had hepatic objective response rate (ORR) of 25% and a hepatic disease control rate (DCR) of 80%. Median PFS and OS were 1.0 and 4.4 months, respectively. Patients with neuroendocrine tumors (NET) had hepatic ORR and DCR of 73% and 100%, respectively. Median PFS was 8.9 months for this cohort. DCR and median PFS and OS for patients with cholangiocarcinoma were 86%, 1.1 months, and 6.7 months, respectively., Conclusions: 90 Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort., Competing Interests: N Fidelman was a recipient of a research grant from Nordion, Inc. (grant term 11/01/2010-10/31/2011), which was used to support this study; the other authors have no conflicts of interest to declare.

Venous thromboembolism (VTE) is an extremely common form of vascular disease and impacts a great number of patients worldwide. Acute deep vein thrombosis (DVT) is a subset of VTE and is traditionally been treated with anticoagulation. There is good quality data which suggests the use of catheter directed interventions for the treatment of acute DVT with the aim of reducing post-thrombotic syndrome (PTS). The present review will discuss the various therapies available for acute DVT, focusing on catheter directed interventions, ranging from traditional anticoagulation to the most novel forms of aspiration thrombectomy., Competing Interests: The authors have no conflicts of interest to declare.

Purpose: To assess safety and efficacy of doxorubicin drug-eluting embolic (DEE) transarterial chemoembolization of hepatocellular carcinoma (HCC) by extrahepatic collateral arteries., Materials and Methods: Records of 177 patients with HCC who underwent 338 consecutive DEE chemoembolization procedures from 2011 to 2014 were retrospectively reviewed. A subgroup of 16 patients (13 men, 3 women, median age 66 y) underwent 24 procedures for 17 HCCs via extrahepatic arteries and was included in the study. Median tumor size was 3.1 cm (range, 1.0-10.3 cm). Extrahepatic collaterals included right inferior phrenic (19 procedures; 12 patients), adrenal (4 procedures; 3 patients), and cystic arteries (2 procedures; 2 patients). Radiographic response was assessed by Modified Response Evaluation Criteria in Solid Tumors criteria. Complications were defined by National Cancer Institute Common Terminology Criteria for Adverse Events., Results: DEE chemoembolization achieved stable disease in 6 (35.3%), partial response in 6 (35.3%), and complete response in 4 (23.5%) HCCs. Disease progression was ultimately observed in 8 tumors (47.1%), with mean time to progression of 8.3 months after chemoembolization (range, 2-13 mo). Three minor and 5 major complications occurred in 8 patients; 2 minor complications were rash in vascular distribution after right inferior phrenic artery DEE chemoembolization. The 5 major complications were transient hepatotoxicity that resolved within 4-80 days; 1 was accompanied by pleural effusion requiring hospitalization. A mean 13.4 months after DEE chemoembolization, 67% of transplant candidates proceeded to liver transplant., Conclusions: DEE transarterial chemoembolization via extrahepatic collaterals was effective and facilitated bridging to transplant. It was generally well tolerated; transient hepatotoxicity was the most common major complication., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

Nonvascular complications represent a significant source of morbidity following renal transplantation and can be seen in up to 20% of patients. Postoperative problems include urinary tract obstruction or leakage and the development of peritransplant fluid collections. Interventional radiologists play a key role in the management of these patients. Image-guided interventions are used to identify the underlying anatomical problem, relieve immediate symptoms, and allow planning for long-term resolution. In this article, we review the urinary tract anatomy relevant to renal transplantation, procedural techniques for image-guided urinary tract interventions and interventions on peritransplant fluid collections, and expected outcomes following image-guided interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Renal transplantation is the therapy of choice in patients with end stage renal disease. Although transplant rejection remains the most common complication after renal transplantation, vascular anatomical complications occur in 1%-23% of renal transplant recipients. Interventional radiologists play an important role in the management of these complications. This review discusses the role of image-guided interventions within the context of multidisciplinary patient management. Particular emphasis is given to anatomical considerations unique to this patient population, techniques used for image-guided interventions, and outcomes of image-guided interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Transjugular intrahepatic portosystemic shunts (TIPS) effectively lower portal pressure and are commonly used to manage selected patients with variceal bleeding. Unfortunately, significant consequences are not infrequently encountered as a result of this diversion of portal venous flow. These consequences include disabling hepatic encephalopathy as well as hepatic decompensation. To manage these complications, therapeutic options include TIPS reduction and TIPS occlusion. TIPS reduction is the favored technique because of the potential for venous thrombosis and recurrent variceal hemorrhage after acute TIPS occlusion. Techniques and indications for TIPS reduction and TIPS occlusion are reviewed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inferior vena cava (IVC) filter placement is indicated for patients with pulmonary embolism and/or deep venous thrombosis when anticoagulation therapy is contraindicated. IVC filter placement, however, is not without complications. In this case, we noted crossing of the filter struts immediately after deployment of the ALN IVC filter (ALN Implants Chirurgicaux Ghisonaccia, France). The filter was then successfully removed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate radiation dose reduction in patients undergoing transarterial chemoembolization with the use of a new image acquisition and processing platform., Materials and Methods: Radiation-dose data were obtained from 176 consecutive chemoembolization procedures in 135 patients performed in a single angiography suite. From January 2013 through October 2013, 85 procedures were performed by using our institution's standard fluoroscopic settings. After upgrading the x-ray fluoroscopy system with an image acquisition and processing platform designed to reduce image noise and reduce skin entrance dose, 91 chemoembolization procedures were performed from November 2013 through December 2014. Cumulative dose-area product (CDAP), cumulative air kerma (CAK), and total fluoroscopy time were recorded for each procedure. Image quality was assessed by three interventional radiologists blinded to the x-ray acquisition platform used., Results: Patient radiation dose indicators were significantly lower for chemoembolization procedures performed with the novel imaging platform. Mean CDAP decreased from 3,033.2 dGy·cm(2) (range, 600.3-9,404.1 dGy·cm(2)) to 1,640.1 dGy·cm(2) (range, 278.6-6,779.9 dGy·cm(2); 45.9% reduction; P < .00001). Mean CAK decreased from 1,445.4 mGy (range, 303.6-5,233.7 mGy) to 971.7 mGy (range, 144.2-3,512.0 mGy; 32.8% reduction; P < .0001). A 20.3% increase in mean total fluoroscopy time was noted after upgrading the imaging platform, but blinded analysis of the image quality revealed no significant degradation., Conclusions: Although a small increase in fluoroscopy time was observed, a significant reduction in patient radiation dose was achieved by using the optimized imaging platform, without image quality degradation., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

The goal of this study was to determine whether the detection of discordant numbers of hypervascular foci at hepatic angiography versus contrast-enhanced (CE) cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)] is associated with adverse clinical outcomes in patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation. We retrospectively reviewed the records of 218 consecutive patients with HCC who were listed for a liver transplant and who underwent transarterial chemoembolization at our institution between January 1, 2006 and December 31, 2010. Patients were grouped into 3 categories: (1) the number of nodules at CT/MRI was concordant with the number of hypervascular foci detected at angiography (n=136), (2) the number of nodules at CT/MRI was greater than the number of hypervascular foci at angiography (n=45), and (3) the number of nodules at CT/MRI was fewer than the number of hypervascular foci at angiography (n=37). The study outcomes were liver transplantation and tumor recurrence after transplantation. The detection of at least 3 more hypervascular foci at angiography versus the number of HCC nodules on CT/MRI was associated with a significantly lower rate of transplantation [multivariate subhazard ratio (SHR), 0.39; 95% confidence interval (CI), 0.17-0.92]. The detection of fewer hypervascular foci at angiography versus the number of HCC nodules on CT/MRI was associated with a significantly higher rate of tumor recurrence after transplantation (multivariate SHR, 3.49; 95% CI, 1.27-9.56). In conclusion, liver transplant candidates with HCC who demonstrate discordant findings between angiography and CE CT or MRI may be at a higher risk for dropout from the transplant list and for tumor recurrence after transplantation., (© 2015 American Association for the Study of Liver Diseases.)

Background: Right adrenal vein (RAV) catheterization can be a very challenging step in adrenal venous sampling (AVS). Visualization of the inferior emissary vein (IEV) may be an indication of successful RAV catheterization., Purpose: To compare the rate of successful RAV sampling in the presence of the IEV., Material and Methods: Retrospective review of all consecutive patients with PA who underwent AVS between April 2009 and April 2012 was performed. A total of 30 patients were identified. Procedural images, cortisol, and aldosterone values obtained from sampling of the RAV and inferior vena cava (IVC) were reviewed. Cortisol measurements obtained from RAV samples were divided by measurements from the infra-renal IVC blood samples in order to calculate the selectivity index (SI). An SI >3 was considered indicative of technically successful RAV sampling., Results: RAV sampling was considered technically successful in 29 out of 30 cases (97%). In cases of successful RAV sampling (29 patients), the IEV was identified in 25 patients (86%). The IEV was visualized in isolation in 16 patients (64%), and in conjunction with visualization of the RAV or right adrenal gland stain in nine patients (36%). The IEV was not visualized in the one case of unsuccessful RAV sampling. Visualizing the IEV had a sensitivity of 86.2% for successful RAV sampling., Conclusion: The IEV may serve as a reliable landmark for the RAV during RAV sampling., (© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of treatment of liver-dominant metastatic gastrointestinal cancer using (90)Y glass microspheres., Methods: Between June 2010 and November 2012, 30 adult patients (22 men, eight women; median age 61 years) with metastatic chemotherapy-refractory unresectable colorectal (n = 15), neuroendocrine (n = 9), intrahepatic cholangiocarcinoma (n = 3), pancreas (n = 2), and esophageal (n = 1) carcinomas underwent 45 lobar or segmental administrations of (90)Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for 6 months after each treatment. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1. Time to maximum response, response duration, progression-free survival (hepatic and extrahepatic), and overall survival were measured., Results: Median target dose and activity were 111.6 Gy and 2.5 GBq per treatment session, respectively. All but three clinical AE were grade 1 or 2 in severity. Serious AE included an unplanned hospital admission for carcinoid crisis, grade 3 vomiting, and grade 4 gastric ulcer. Patients with colorectal cancer had hepatic objective response rate (ORR) of 27 % and a disease control rate (DCR) of 73 %. Median progression-free and overall survival were 1.0 and 4.9 months, respectively. Patients with neuroendocrine tumors had hepatic ORR and DCR of 78 % and 100 %, respectively. Median progression-free survival was 18.5 months for this cohort., Conclusions: Y glass microspheres device has a favorable safety profile and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort.

Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS)., Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modified response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented., Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation., Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.

Purpose: To determine clinical outcomes of patients who underwent imaging-guided percutaneous drainage of breast fluid collections after mastectomy and breast reconstruction., Materials and Methods: A retrospective review was performed including all consecutive patients who underwent percutaneous drainage of fluid collections after mastectomy with tissue expander-based reconstruction between January 2007 and September 2012. During this period, 879 mastectomies (563 patients) with expander-based breast reconstruction were performed. Fluid collections developed in 28 patients (5%), which led to 30 imaging-guided percutaneous drainage procedures. The median follow-up time was 533 days. Patient characteristics, surgical technique, microbiology analysis, and clinical outcomes were reviewed., Results: The mean age of patients was 51.5 years (range, 30.9-69.4 y), and the median time between breast reconstruction and drainage was 35 days (range, 4-235 d). Erythema and swelling were the most common presenting symptoms. The median volume of fluid evacuated at the time of drain placement was 70 mL. Drains were left in place for a median 14 days (range, 6-34 d). Microorganisms were detected in the fluid in 12 of 30 drainage procedures, with Staphylococcus aureus being the most common microorganism. No further intervention was needed in 21 of 30 drainage procedures (70%). However, surgical intervention (removal of expanders) was needed after 6 (20%) drainage procedures, and additional percutaneous drainage procedures were performed after 3 (10%) drainage procedures., Conclusions: Percutaneous drainage is an effective means of treating postoperative fluid collections after expander-based breast reconstruction and can obviate the need for repeat surgery in most cases., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to test the potential of clinical imaging modalities, 64-slice multidetector computed tomography (MDCT) and 1.5T magnetic resonance imaging (MRI) for qualitative and quantitative evaluation of acute microinfarcts and to determine the effects of <120 μm microemboli on left ventricular function, perfusion, cardiac injury biomarkers, arrhythmia, and cellular and vascular structures. Under X-ray fluoroscopy, 40-120 μm (16 mm(3) ) microemboli were delivered to embolize the left anterior descending (LAD) coronary artery of nine pigs. MDCT/MRI were performed at 72 h in a single session. Microinfarcts were visible in six of nine animals on delayed contrast-enhanced MDCT/MR images but measurable in all animals using semiautomated threshold methods. Other MDCT and MRI sequences demonstrated decline in left ventricular ejection fraction, regional strain and perfusion in visible and invisible microinfarcted regions. Microemboli caused significant elevation in cardiac injury enzymes and arrhythmias. Various sizes of microinfarcts appeared microscopically as distinct aggregates of macrophages replacing myocardium. Semiautomated threshold methods are necessary to measure and confirm/deny the presence of myocardial microinfarcts. This study offers support for alternative applications of MDCT/MRI in assessing clinical cases in which microemboli <120 μm escape protective devices during percutaneous coronary interventions. Although microembolization resulted in no mortality, it caused left ventricular dysfunction, perfusion deficit, cellular damage increase in cardiac injury enzymes, and arrhythmias., (Copyright © 2011 Wiley Periodicals, Inc.)

Proinflammatory T helper 1 (Th1) cells express high levels of carbohydrate ligands for the endothelial selectins, but the molecular basis for this phenotype is incompletely understood. We document here a significant role in selectin ligand formation for the recently described Th1 transcription factor T-bet. Th1 cells generated from T-bet-/- mice showed significantly lower levels of ligands for both E-selectin and P-selectin, compared with wild-type (WT) Th1 cells. Enforced expression of T-bet in WT Th0 cells only modestly up-regulated P-selectin ligands and had no effect on E-selectin ligands. To define a mechanism for the defects observed in T-bet-/- mice, we examined expression of glycosyltransferases involved in selectin ligand biosynthesis. T-bet-/- Th1 cells expressed significantly lower levels of core 2 beta1,6 N-acetylglucosaminyltransferase I (C2GlcNAcT-I), but no differences in levels of alpha 2,3-sialyltransferase IV (ST3Gal-IV). Further, we show that T-bet is responsible for the signal transducer and activator of transcription 4 (Stat4)-independent increase in Th1 cells of fucosyltransferase VII (FucT-VII). We also identify ST3Gal-VI, which is thought to play an important role in E- and P-selectin ligand formation, as an interleukin 12 (IL-12)-regulated, T-bet-dependent gene. These data show that T-bet controls selectin ligand formation in Th1 cells via control of expression of multiple key enzymes in response to IL-12 signaling and establishes an independent transcriptional pathway for control of Th1 cell traffic.

Antibody-secreting plasma cells represent the critical end-stage effector cells of the humoral immune response. Here, we show that several distinct plasma cell subsets are concurrently present in the lymph nodes, spleen, and bone marrow of mice deficient in both E- and P-selectin. One of these subsets was a B220-negative immunoglobulin g (IgG) plasma cell population expressing low to negative surface levels of syndecan-1. Examination of the chemotactic responsiveness of IgG plasma cell subsets revealed that migration toward stromal cell-derived factor 1/CXC ligand 12 (SDF-1/CXCL12) was primarily limited to the B220-lo subset regardless of tissue source. Although B220-negative plasma cells did not migrate efficiently in response to CXCL12 or to other chemokines for which receptor mRNA was expressed, these cells expressed substantial surface CXC chemokine receptor-4 (CXCR4), and CXCL12 stimulation rapidly induced extracellular signal regulated kinase 1 (ERK1)/ERK2 phosphorylation, demonstrating that CXCR4 retained signaling capacity. Therefore, B220-negative plasma cells exhibit a selective uncoupling of chemokine receptor expression and signaling from migration. Taken together, our findings document the presence of significant heterogeneity within the plasma cell compartment, which suggests a complex step-wise scheme of plasma cell differentiation in which the degree of differentiation and tissue location can influence the chemotactic responsiveness of IgG plasma cells.