Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Driving Patients Crazy: Acute Neuropsychiatric Toxicities of Commonly Prescribed Antibiotics in IR.

Neuropsychiatric toxicities are uncommon but well-documented side effects of antibiotics. Society of Interventional Radiology guidelines recommend various antibiotic regimens for patients undergoing interventional radiological procedures. These same classes of drugs are also used to treat infectious complications in patients. Antibiotics have a wide spectrum of affective and cognitive toxicities, the most severe of which can lead to hospitalization or suicide. Fluoroquinolones have the highest incidence of these toxicities.

Mitigation of Sarcopenia after Peritoneovenous Shunt Placement in Patients with Refractory Ascites.

PURPOSE: To evaluate the effect of peritoneonvenous shunt placement on metrics of sarcopenia in patients with refractory ascites. MATERIALS AND METHODS: An institutional review board-approved single-institution retrospective analysis of all patients who underwent peritoneovenous shunt (Denver Shunt; BD, Franklin Lakes, New Jersey) placement (N = 29) and a comparator cohort of patients with cirrhosis who underwent serial paracentesis (N = 42) from 2009 to 2019 with baseline and follow-up cross-sectional imaging of at least 3 months was performed. Axial muscle area measurements (psoas, paraspinal, and total abdominal wall) were performed using free-hand region-of-interest technique. Patient records were reviewed for demographic characteristics, referring indication, laboratory studies, and performance status. Statistical analyses were performed with Student t test, Welch unequal variances, Fisher exact test, and Wilcoxon signed rank test. RESULTS: The most common indications for peritoneovenous shunt placement were metastatic disease or cirrhosis. In the shunt cohort, there were no significant differences in the aggregate psoas muscle area (13.4 vs 14.0 cm2; P = .223) or paraspinal muscle area (43.0 vs 42.2 cm2; P = .471). In the paracentesis cohort, there were significant decreases in aggregate psoas (18.1 vs 15.7 cm2; P < .0001) and erector spinae (43.4 vs 39.9 cm2; P < .0001) muscle area. In addition, there was a significant decrease in serum albumin level (3.2 vs 3.0 g/dL; P = .015) and Eastern Cooperative Oncology Group performance status score (1.0 vs 1.3; P < .0001) in the paracentesis group, compared with no significant changes in the shunt cohort. CONCLUSIONS: In patients with refractory ascites who are not candidates for transjugular intrahepatic portosystemic shunt placement, peritoneovenous shunt mitigates loss of truncal muscle and, in some instances, promotes muscle growth.

Transarterial Embolization Modulates the Immune Response within Target and Nontarget Hepatocellular Carcinomas in a Rat Model.

Background Transarterial embolization (TAE) is the most common treatment for hepatocellular carcinoma (HCC); however, there remain limited data describing the influence of TAE on the tumor immune microenvironment. Purpose To characterize TAE-induced modulation of the tumor immune microenvironment in a rat model of HCC and identify factors that modulate this response. Materials and Methods TAE was performed on autochthonous HCCs induced in rats with use of diethylnitrosamine. CD3, CD4, CD8, and FOXP3 lymphocytes, as well as programmed cell death protein ligand-1 (PD-L1) expression, were examined in three cohorts: tumors from rats that did not undergo embolization (control), embolized tumors (target), and nonembolized tumors from rats that had a different target tumor embolized (nontarget). Differences in immune cell recruitment associated with embolic agent type (tris-acryl gelatin microspheres [TAGM] vs hydrogel embolics) and vascular location were examined in rat and human tissues. A generalized estimating equation model and t, Mann-Whitney U, and χ2 tests were used to compare groups. Results Cirrhosis-induced alterations in CD8, CD4, and CD25/CD4 lymphocytes were partially normalized following TAE (CD8: 38.4%, CD4: 57.6%, and CD25/CD4: 21.1% in embolized liver vs 47.7% [P = .02], 47.0% [P = .01], and 34.9% [P = .03], respectively, in cirrhotic liver [36.1%, 59.6%, and 4.6% in normal liver]). Embolized tumors had a greater number of CD3, CD4, and CD8 tumor-infiltrating lymphocytes relative to controls (191.4 cells/mm2 vs 106.7 cells/mm2 [P = .03]; 127.8 cells/mm2 vs 53.8 cells/mm2 [P < .001]; and 131.4 cells/mm2 vs 78.3 cells/mm2 [P = .01]) as well as a higher PD-L1 expression score (4.1 au vs 1.9 au [P < .001]). A greater number of CD3, CD4, and CD8 lymphocytes were found near TAGM versus hydrogel embolics (4.1 vs 2.0 [P = .003]; 3.7 vs 2.0 [P = .01]; and 2.2 vs 1.1 [P = .03], respectively). The number of lymphocytes adjacent to embolics differed based on vascular location (17.9 extravascular CD68+ peri-TAGM cells vs 7.0 intravascular [P < .001]; 6.4 extravascular CD68+ peri-hydrogel embolic cells vs 3.4 intravascular [P < .001]). Conclusion Transarterial embolization-induced dynamic alterations of the tumor immune microenvironment are influenced by underlying liver disease, embolic agent type, and vascular location. © RSNA, 2022 Online supplemental material is available for this article. See also the editorials by Kennedy et al and by White in this issue.

Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease.

OBJECTIVES: Hepatic venous pressure gradient (HVPG) is considered the standard in quantifying portal hypertension, but can be unreliable in dialysis patients. A noninvasive ultrasound technique, subharmonic-aided pressure estimation (SHAPE), may be a valuable surrogate of these pressure estimates. This study compared SHAPE and HVPG with pathology findings for fibrosis in dialysis patients. METHODS: This was a subgroup study from an IRB-approved trial that included 20 patients on dialysis undergoing SHAPE examinations of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI), during infusion of Sonazoid (GE Healthcare, Oslo, Norway). SHAPE was compared to HVPG and pathology findings using the Ludwig-Batts scoring system for fibrosis. Logistic regression, ROC analysis, and t-tests were used to compare HVPG and SHAPE with pathological findings of fibrosis. RESULTS: Of 20 cases, 5 had HVPG values corresponding to subclinical and clinical portal hypertension (≥6 and ≥10 mmHg, respectively) while 15 had normal HVPG values (≤5 mmHg). SHAPE and HVPG correlated moderately (r = 0.45; P = .047). SHAPE showed a trend toward correlating with fibrosis (r = 0.42; P = .068), while HVPG did not (r = 0.18; P = .45). SHAPE could differentiate between mild (stage 0-1) and moderate to severe (stage 2-4) fibrosis (-10.4 ± 4.9 dB versus -5.4 ± 3.2 dB; P = .035), HVPG could not (3.0 ± 0.6 mmHg versus 4.8 ± 0.7 mmHg; P = .30). ROC curves showed a diagnostic accuracy for SHAPE of 80%, while HVPG reached 76%. CONCLUSION: Liver fibrosis staging in dialysis patients evaluated for portal hypertension appears to be more accurately predicted by SHAPE than by HVPG; albeit in a small sample size.

Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent.

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.

A Water-Based Liquid Embolic: Evaluation of its Safety and Efficacy in a Rabbit Kidney Model.

PURPOSE: To evaluate a novel aqueous-based liquid embolic (Embrace Hydrogel Embolic System, [HES]) that has been developed to embolize hypervascular tumors by filling the tumor vascular bed and solidifying into a hydrogel. HES was evaluated for embolization safety and efficacy relative to microspheres in a preclinical rabbit kidney model. MATERIALS AND METHODS: A renal embolization model in New Zealand white rabbits was utilized. Twenty-four rabbits underwent unilateral kidney embolization via the main renal artery with either HES or 40-µm microspheres. Twenty-two rabbits survived the procedure and were monitored for 2, 12, 17.5, or 26 weeks before sacrifice. All rabbits underwent a repeat renal angiogram before necropsy. HES was evaluated for nontarget embolization, safety, and embolization effectiveness as measured by recanalization and viability of embolized tissue. RESULTS: Both embolization materials were found to be safe, with targeted tissue necrosis and absence of nontarget embolization. Prenecropsy angiograms found vascular recanalization in 0/14 (0%) HES-embolized kidneys and in 3/8 (38%) microsphere-embolized kidneys (P = .036). Viable kidney tissue was observed in 2/14 (14%) kidneys embolized with HES and 5/8 (63%) kidneys embolized with microspheres (P = .052). All kidneys embolized with microspheres that showed vascular recanalization had viable tissue on histological sections. HES was observed in vessels as small as 10 µm in diameter in histological analysis. CONCLUSIONS: HES provided deep, durable vascular bed embolization that resulted in less recanalization and, on an average, less viable target tissue compared with 40-µm microspheres. No systemic effects or nontarget tissue embolization was identified.

Radiologically Placed Peritoneovenous Shunt is an Acceptable Treatment Alternative for Refractory Ascites Due to End-Stage Liver Disease.

PURPOSE: To compare patients treated with large-volume paracentesis (LVP), transjugular intrahepatic portosystemic shunt (TIPS), and peritoneovenous shunt (PVS) for ascites. MATERIALS AND METHODS: A retrospective study of 192 patients treated with LVP (94), TIPS (75), or PVS (23) was performed. Records were reviewed for patient characteristics and outcomes. The patients' age differed (LVP, 59.5 years; TIPS, 58.8 years; and PVS, 65.6 years; P = .003). Nonalcoholic steatohepatitis was the most common etiology in the PVS cohort (11/23, 47%), and hepatitis C in the TIPS (27/75, 36%), and LVP cohorts (43/94, 46%) (P = .032). The model for end-stage liver disease score was significantly different (LVP, 14; TIPS, 13; and PVS, 8; P = .035). Hepatocellular carcinoma was higher in the PVS cohort (6/23 patients, 25%) than in the TIPS (4/75, 5%), and LVP (12/94, 12%) cohorts (P = .03). RESULTS: Emergency department visits and hospital readmissions were the highest in the LVP cohort (40%, ≥2 readmissions, P < .001). Patients required fewer LVPs after TIPS (1.5 to 0.14, P < .001) or PVS (2.1 to 0.5, P = .019). In an unadjusted Cox model, patients in the TIPS cohort were found to have a 58% reduction in the risk of death compared with patients in the LVP cohort (P = .003). Transplant-free survival (PVS, 44 days; TIPS, 155 days; and LVP, 213 days) differed (log rank = 0.001). CONCLUSIONS: The survival in the PVS and TIPS cohorts was similar, with less healthcare utilization than the LVP cohort. PVS is a satisfactory alternative to LVP.

Infection Rates Following Hepatic Embolotherapy in Patients with Prior Biliary Interventions: Comparison of Single-Drug Moxifloxacin and Multidrug Antibiotic Prophylaxis.

PURPOSE: To investigate the incidence of infection in patients with prior biliary interventions undergoing hepatic embolotherapy following extended antibiotic prophylaxis using moxifloxacin monotherapy or a multidrug regimen. MATERIAL AND METHODS: Under an Institutional Review Board-approved protocol, retrospective review of a quality assurance database identified all liver-directed therapies (LDTs) at a tertiary care center between 2010 and 2019 with biliary intervention prior to LDT Records were reviewed for infectious complications within 3 months of chemo- or radioembolization. Patients were categorized based on extended antibiotic prophylaxis regimen: oral moxifloxacin monotherapy or multidrug regimen of levofloxacin and metroniodazole plus preprocedural neomycin and erythromycin. Procedures without at least 2 months of clinical follow-up, hepatic ablation, and procedures without extended antibiotic prophylaxis were excluded Regression analysis was used to analyze multivariate data to detect a difference in infection rate. RESULTS: Twenty-four chemoembolization and 58 radioembolization procedures were performed on 55 patients with prior biliary interventions. Forty-four used monotherapy and 38 used multidrug regimen. The incidence of infection was 16.7% (4/24) after chemoembolization and 13.8% (8/58) after radioembolization The incidence of infection in patients did not differ between antibiotic prophylaxis regimens (18.2% [8/44] with moxifloxacin monotherapy and 10.5% [4/38] multidrug regimen, P = .3) or between types of biliary interventions (24.1% [7/29] with bilioenteric anastomosis and 23.8% [5/21] biliary stenting, P = .3). CONCLUSIONS: The types of extended antibiotic prophylaxis (moxifloxacin monotherapy vs multitherapy), prior biliary intervention, and embolotherapy were not found to be associated with differences in the incidence of infectious complications in this population.

Musculoskeletal Oncologic Interventions: Proceedings from the Society of Interventional Radiology and Society of Interventional Oncology Research Consensus Panel.

Musculoskeletal interventions are increasingly used with palliative and curative intent in the multidisciplinary treatment of oncology patients with bone and soft-tissue tumors. There is an unmet need for high-quality evidence to guide broader application and adoption of minimally invasive interventional technologies to treat these patients. Therefore, the Society of Interventional Radiology Foundation and the Society of Interventional Oncology collaborated to convene a research consensus panel to prioritize a research agenda addressing the gaps in the current evidence. This article summarizes the panel's proceedings and recommendations for future basic science and clinical investigation to chart the course for interventional oncology within the musculoskeletal system. Key questions that emerged addressed the effectiveness of ablation within specific patient populations, the effect of combination of ablation with radiotherapy and/or immunotherapy, and the potential of standardization of techniques, including modeling and monitoring, to improve the consistency and predictability of treatment outcomes.

Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension.

BACKGROUND: Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression. AIMS: To determine whether the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension. METHODS: This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care. RESULTS: Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n = 31) and clinical (n = 33) portal hypertension (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66. CONCLUSION: The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.

Abnormal Pretreatment Liver Function Tests Are Associated with Discontinuation of Peptide Receptor Radionuclide Therapy in a U.S.-Based Neuroendocrine Tumor Cohort.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is effective for treating midgut neuroendocrine tumors (NETs); however, incorporation of PRRT into routine practice in the U.S. is not well studied. Herein we analyze the first year of PRRT implementation to determine tolerance of PRRT and factors that increase risk of PRRT discontinuation. MATERIALS AND METHODS: Medical records were reviewed and data were abstracted on all patients with NETs scheduled for PRRT during the first year of PRRT implementation at a U.S. NET referral center (August 2018 through July 2019). Logistic regression was used to identify factors associated with PRRT discontinuation. RESULTS: Fifty-five patients (56% male) were scheduled for PRRT over the study period. The most common primary NET location was small bowel (47%), followed by pancreas (26%), and 84% of the NETs were World Health Organization grade 1 or 2. The cohort was heavily pretreated with somatostatin analog (SSA) therapy (98%), non-SSA systemic therapy (64%), primary tumor resection (73%), and liver-directed therapy (55%). At the time of analysis, 52 patients completed at least one PRRT treatment. Toxicities including bone marrow suppression and liver function test (LFT) abnormalities were comparable to prior publications. Eleven patients (21%) prematurely discontinued PRRT because of toxicity or an adverse event. Pretreatment LFT abnormality was associated with increased risk of PRRT cancellation (odds ratio: 12; 95% confidence interval: 2.59-55.54; p < .001). CONCLUSION: PRRT can be administered to a diverse NET population at a U.S. NET referral center. Baseline liver function test abnormality increases the likelihood of PRRT discontinuation. IMPLICATIONS FOR PRACTICE: Peptide receptor radionuclide therapy (PRRT) can be successfully implemented at a U.S. neuroendocrine tumor (NET) referral center in a NET population that is diverse in tumor location, grade, and prior treatment history. Toxicity and adverse effects of PRRT are comparable to prior reports; however, 21% of individuals prematurely discontinued PRRT. Patients with baseline liver function test abnormalities were more likely to discontinue PRRT than patients with normal liver function tests, which should be taken into consideration when selecting treatment options for NETs.

Deep Learning Based on MRI for Differentiation of Low- and High-Grade in Low-Stage Renal Cell Carcinoma.

Pretreatment determination of renal cell carcinoma aggressiveness may help to guide clinical decision-making. PURPOSE: To evaluate the efficacy of residual convolutional neural network using routine MRI in differentiating low-grade (grade I-II) from high-grade (grade III-IV) in stage I and II renal cell carcinoma. STUDY TYPE: Retrospective. POPULATION: In all, 376 patients with 430 renal cell carcinoma lesions from 2008-2019 in a multicenter cohort were acquired. The 353 Fuhrman-graded renal cell carcinomas were divided into a training, validation, and test set with a 7:2:1 split. The 77 WHO/ISUP graded renal cell carcinomas were used as a separate WHO/ISUP test set. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T/T2 -weighted and T1 contrast-enhanced sequences. ASSESSMENT: The accuracy, sensitivity, and specificity of the final model were assessed. The receiver operating characteristic (ROC) curve and precision-recall curve were plotted to measure the performance of the binary classifier. A confusion matrix was drawn to show the true positive, true negative, false positive, and false negative of the model. STATISTICAL TESTS: Mann-Whitney U-test for continuous data and the chi-square test or Fisher's exact test for categorical data were used to compare the difference of clinicopathologic characteristics between the low- and high-grade groups. The adjusted Wald method was used to calculate the 95% confidence interval (CI) of accuracy, sensitivity, and specificity. RESULTS: The final deep-learning model achieved a test accuracy of 0.88 (95% CI: 0.73-0.96), sensitivity of 0.89 (95% CI: 0.74-0.96), and specificity of 0.88 (95% CI: 0.73-0.96) in the Fuhrman test set and a test accuracy of 0.83 (95% CI: 0.73-0.90), sensitivity of 0.92 (95% CI: 0.84-0.97), and specificity of 0.78 (95% CI: 0.68-0.86) in the WHO/ISUP test set. DATA CONCLUSION: Deep learning can noninvasively predict the histological grade of stage I and II renal cell carcinoma using conventional MRI in a multiinstitutional dataset with high accuracy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization.

PURPOSE: To compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET). MATERIALS AND METHODS: This study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above. RESULTS: Chronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4-5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005). CONCLUSIONS: Delayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.

Prospective Study of Systemic Yttrium-90 Elution during Radioembolization of Hepatic Metastases.

PURPOSE: To evaluate total blood radioactivity (BR) after SIR-Spheres yttrium-90 (90Y) radioembolization and differences in BR based on delivery method. MATERIALS AND METHODS: Twenty participants with hepatic metastases undergoing first radioembolization were prospectively enrolled from December 2017 to June 2018. Blood samples were drawn at baseline and 0, 10, 20, 60, and 120 minutes after 90Y administration. BR was measured with a γ-counter and scaled by estimated blood volume. Percentage of instilled radioactivity in the bloodstream was calculated as area under the fitted curve, and differences between delivery methods were examined with nonparametric statistical tests. RESULTS: In 10 participants, resin microspheres were instilled with 50% Isovue 300 diluted in saline solution in the D line, and 10 others were treated with dextrose 5% in water (D5W) in the D line. Median administered activities were 944 MBq (range, 746-1,993 MBq) and 1,213 MBq (range, 519-2,066 MBq), respectively. Fraction of 90Y in blood was significantly higher with dilute contrast agent than with D5W (median, 0.5% of injected activity vs 0.2%; P = .001). Among all participants, the maximum activity delivered was 2,066 MBq, and a maximum of 1% of administered radioactivity was measured as free 90Y in blood. Assuming these highest-case values and complete decay of all free 90Y in bone, a dose to red marrow of 132.3 mGy was calculated by Organ Level INternal Dose Assessment/EXponential Modeling. CONCLUSIONS: Blood sampling after radioembolization allowed for estimation of the time-activity curve and BR. Delivery with 50% contrast agent in saline solution resulted in a significant increase in BR vs D5W, even though the total BR for both groups was nominal.

Curative-Intent Therapies in Localized Hepatocellular Carcinoma.

PURPOSE OF REVIEW: The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvants preparing patients for curative treatment. RECENT FINDINGS: For HCC < 3 cm, percutaneous thermal ablation provides oncologic outcomes similar to surgical resection and is now a recommended first-line therapy in the EASL guidelines. Both ablation and embolization are recommended as bridging therapies for HCC patients awaiting liver transplantation. T3 HCC can be downstaged by embolization to T2, allowing liver transplantation with similar outcomes to patients transplanted within Milan criteria. New and evolving techniques such as SBRT, radiation segmentectomy and lobectomy, and combination therapies show promise but require further prospective data before they can be integrated into treatment algorithms. Combinations of embolic, ablative, and extirpative therapies can increase access to curative-intent treatment of HCC. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location, and underlying liver cirrhosis.

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers.

This phase I study investigated the safety and activity of lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin (CART-meso) in patients with malignant pleural mesothelioma, ovarian carcinoma, and pancreatic ductal adenocarcinoma. Fifteen patients with chemotherapy-refractory cancer (n = 5 per indication) were treated with a single CART-meso cell infusion. CART-meso cells were engineered by lentiviral transduction with a construct composed of the anti-mesothelin single-chain variable fragment derived from the mouse monoclonal antibody SS1 fused to intracellular signaling domains of 4-1BB and CD3zeta. Patients received 1-3 × 107 or 1-3 × 108 CART-meso cells/m2 with or without 1.5 g/m2 cyclophosphamide. Lentiviral-transduced CART-meso cells were well tolerated; one dose-limiting toxicity (grade 4, sepsis) occurred at 1-3 × 107/m2 CART-meso without cyclophosphamide. The best overall response was stable disease (11/15 patients). CART-meso cells expanded in the blood and reached peak levels by days 6-14 but persisted transiently. Cyclophosphamide pre-treatment enhanced CART-meso expansion but did not improve persistence beyond 28 days. CART-meso DNA was detected in 7/10 tumor biopsies. Human anti-chimeric antibodies (HACA) were detected in the blood of 8/14 patients. CART-meso cells were well tolerated and expanded in the blood of all patients but showed limited clinical activity. Studies evaluating a fully human anti-mesothelin CAR are ongoing.

Inferior Vena Cava Reconstruction in Symptomatic Patients Using Palmaz Stents: A Retrospective Single-Center Experience.

BACKGROUND: The use of stents for treating central venous occlusion is well described. Limited evidence exists related to Palmaz balloon-expandable stent use in inferior vena cava (IVC) reconstruction. We analyzed patency and complication rates after IVC reconstruction using Palmaz stents. METHODS: From 2002 to 2019, 37 patients (mean age: 51 year) underwent IVC reconstruction with 68 Palmaz stents. Indications were symptomatic chronic venous obstruction in the infrarenal (n = 25) and intrahepatic (n = 12) IVC. Demographic, operative, and imaging data were evaluated. Clinical data, abdominal CT, and/or duplex ultrasound were used to determine patency at follow-up. RESULTS: Restoration of caval patency was achieved in all patients, with complications in 2/37 (5.4%) patients (thrombus formation within the stent; stent embolization eight days after placement). Follow-up data were available for 27 patients. Primary patency was maintained through last follow-up in 19/27 (70%) patients (mean: 1.1 year), with successful stent redilation performed in 6 patients. Mean duration of primary-assisted patency (n = 5) was 1.2 year. Late lumen loss was (n = 13) was 40% during a mean time to follow-up of 2.0 years. Primary patency in patients with occlusion secondary to malignancy was 109 day (range: 1 day-1.0 year), whereas primary patency in patients with occlusion from other etiologies was 1.1 year (range: 2 day-5.9 year). The Kaplan-Meier analysis demonstrated primary and primary-assisted patency of 66% and 84%, respectively, at 24 and 48 months. CONCLUSIONS: Palmaz balloon-expandable stents for IVC reconstruction is feasible and effective for symptomatic IVC occlusion. Risk of stent migration was low.

Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell-mediated immunotherapy. We engineered T cells to transiently express a messenger RNA encoding a chimeric antigen receptor (CAR) specific for mesothelin, a protein that is overexpressed by PDAC cells. We performed a phase I study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly for 3 weeks. None of the patients developed cytokine release syndrome or neurologic symptoms and there were no dose-limiting toxicities. Disease stabilized in 2 patients, with progression-free survival times of 3.8 and 5.4 months. We used 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography imaging to monitor the metabolic active volume (MAV) of individual tumor lesions. The total MAV remained stable in 3 patients and decreased by 69.2% in 1 patient with biopsy-proven mesothelin expression; in this patient, all liver lesions had a complete reduction in FDG uptake at 1 month compared with baseline, although there was no effect on the primary PDAC. Transient CAR expression was detected in patients' blood after infusion and led to expansion of new immunoglobulin G proteins. Our results provide evidence for the potential antitumor activity of messenger RNA CARTmeso cells, as well as PDAC resistance to the immune response.