Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas.

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.

Society of Interventional Radiology Position Statement on the Endovascular Management of Acute Iliofemoral Deep Vein Thrombosis.

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.

Society of Interventional Radiology Position Statement on the Management of Chronic Iliofemoral Venous Obstruction with Endovascular Placement of Metallic Stents.

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.

Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study.

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.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

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 m2 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.

Fine-Needle Aspiration Biopsy of Liver Lesions Yields Higher Tumor Fraction for Molecular Studies: A Direct Comparison With Concurrent Core Needle Biopsy.

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.

Surgical, Interventional, and Medical Palliation of Portal Hypertension.

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.

Interventional Management of Nonvascular Renal Transplant Complications.

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.

Interventional Management of Vascular Renal Transplant Complications.

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.