Response assessment methods for patients with hepatic metastasis from rare tumor primaries undergoing transarterial chemoembolization.

PURPOSE: This study assessed the response to conventional transarterial chemoembolization (cTACE) in patients with liver metastases from rare tumor primaries using one-dimensional (1D) and three-dimensional (3D) quantitative response assessment methods, and investigate the relationship of lipiodol deposition in predicting response. MATERIALS AND METHODS: This retrospective bicentric study included 16 patients with hepatic metastases from rare tumors treated with cTACE between 2002 and 2017. Multi-phasic MR imaging obtained before and after cTACE was used for assessment of response. Response evaluation criteria in solid tumors (RECIST) and modified-RECIST (mRECIST) were utilized for 1D response assessment, and volumetric RECIST (vRECIST) and enhancement-based quantitative European Association for Study of the Liver EASL (qEASL) were used for 3D response assessment. The same day post-cTACE CT scan was analyzed to quantify intratumoral lipiodol deposition (%). RESULTS: The mean and standard deviation (SD) of diameter of treated lesions per targeted area was 7.5 ± 5.4 cm, and the mean and SD of number of metastases in each targeted area was 4.2 ± 4.6. cTACE was technically successful in all patients, without major complications. While RECIST and vRECIST methods did not allocate patients with partial response, mRECIST and qEASL identified patients with partial response. Intratumoral lipiodol deposition significantly predicted treatment response according qEASL (R2 = 0.470, p < 0.01), while no association was shown between lipiodol deposition within treated tumor area and RECIST or mRECIST (p > 0.212). CONCLUSION: 3D quantitative volumetric response analysis can be used for stratification of response to cTACE in patients with hepatic metastases originating from rare primary tumors. Lipiodol deposition could potentially be used as an early surrogate to predict response to cTACE.

Lipiodol Deposition and Washout in Primary and Metastatic Liver Tumors After Chemoembolization.

BACKGROUND/AIM: Lipiodol is the key component of conventional trans-arterial chemoembolization. Our aim was to evaluate lipiodol deposition and washout rate after conventional trans-arterial chemoembolization in intrahepatic cholangiocarcinoma and hepatic metastases originating from neuroendocrine tumors and colorectal carcinoma. PATIENTS AND METHODS: This was a retrospective analysis of 44 patients with intrahepatic cholangiocarcinoma and liver metastasis from neuroendocrine tumors or colorectal carcinoma who underwent conventional trans-arterial chemoembolization. Lipiodol volume (cm3) was analyzed on non-contrast computed tomography imaging obtained within 24 h post conventional trans-arterial chemoembolization, and 40-220 days after conventional trans-arterial chemoembolization using volumetric image analysis software. Tumor response was assessed on contrast-enhanced magnetic resonance imaging 1 month after conventional trans-arterial chemoembolization. RESULTS: The washout rate was longer for neuroendocrine tumors compared to colorectal carcinoma, with half-lives of 54.61 days (p<0.00001) and 19.39 days (p<0.001), respectively, with no exponential washout among intrahepatic cholangiocarcinomas (p=0.83). The half-life for lipiodol washout was longer in tumors larger than 300 cm3 compared to smaller tumors (25.43 vs. 22.71 days). Lipiodol wash out half-life was 54.76 days (p<0.01) and 29.45 days (p<0.00001) for tumors with a contrast enhancement burden of 60% or more and less than 60%, respectively. A negative exponential relationship for lipiodol washout was observed in non-responders (p<0.00001). CONCLUSION: Lipiodol washout is a time-dependent process, and occurs faster in colorectal carcinoma tumors, tumors smaller than 300 cm3, tumors with baseline contrast enhancement burden of less than 60%, and non-responding target lesions.

Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial.

BACKGROUND: The use of the ethiodized oil- Lipiodol in conventional trans-arterial chemoembolization (cTACE) ensures radiopacity to visualize drug delivery in the process of providing selective drug targeting to hepatic cancers and arterial embolization. Lipiodol functions as a carrier of chemo drugs for targeted therapy, as an embolic agent, augmenting the drug effect by efflux into the portal veins as well as a predictor for the tumor response and survival. PURPOSE: To prospectively evaluate the role of 3D quantitative assessment of intra-procedural Lipiodol deposition in liver tumors on CBCT immediately after cTACE as a predictive biomarker for the outcome of cTACE. MATERIALS & METHODS: This was a post-hoc analysis of data from an IRB-approved prospective clinical trial. Thirty-two patients with hepatocellular carcinoma or liver metastases underwent contrast enhanced CBCT obtained immediately after cTACE, unenhanced MDCT at 24 h after cTACE, and follow-up imaging 30-, 90- and 180-days post-procedure. Lipiodol deposition was quantified on CBCT after cTACE and was characterized by 4 ordinal levels: ≤25%, >25-50%, >50-75%, >75%. Tumor response was assessed on follow-up MRI. Lipiodol deposition on imaging, correlation between Lipiodol deposition and tumor response criteria, and correlation between Lipiodol coverage and median overall survival (MOS) were evaluated. RESULTS: Image analysis demonstrated a high degree of agreement between the Lipiodol deposition on CBCT and the 24 h post-TACE CT, with a Bland-Altman plot of Lipiodol deposition on imaging demonstrated a bias of 2.75, with 95%-limits-of-agreement: -16.6 to 22.1%. An inverse relationship between Lipiodol deposition in responders versus non-responders for two-dimensional EASL reached statistical significance at 30 days (p = 0.02) and 90 days (p = 0.05). Comparing the Lipiodol deposition in Modified Response Evaluation Criteria in Solid Tumors (mRECIST) responders versus non-responders showed a statistically significant higher volumetric deposition in responders for European Association for the Study of the Liver (EASL)-30d, EASL-90d, and quantitative EASL-180d. The correlation between the relative Lipiodol deposition and the change in enhancing tumor volume showed a negative association post-cTACE (30-day: p < 0.001; rho = -0.63). A Kaplan-Meier analysis for patients with high vs. low Lipiodol deposition showed a MOS of 46 vs. 33 months (p = 0.05). CONCLUSION: 3D quantification of Lipiodol deposition on intra-procedural CBCT is a predictive biomarker of outcome in patients with primary or metastatic liver cancer undergoing cTACE. There are spatial and volumetric agreements between 3D quantification of Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT could suggest that acquiring MDCT 24 h after cTACE is redundant. Importantly, the demonstrated relationship between levels of tumor coverage with Lipiodol and degree and timeline of tumor response after cTACE underline the role of Lipiodol as an intra-procedural surrogate for tumor response, with potential implications for the prediction of survival.

Dual-chambered venous access port as alternative access for extracorporeal apheresis therapy.

PURPOSE: To evaluate the use of a dual-chambered venous access port for extracorporeal apheresis therapy. METHODS: This was a single-center retrospective analysis of all patients who received a dual-chambered venous access port for apheresis therapy over a 36-month period. Clinical success was defined as successful completion of at least one round of apheresis via the venous access port. Major complications were defined as any event requiring elevation of patient care and/or venous access port removal or repositioning. Minor complications were defined as venous access port issues resolved with clinical intervention. RESULTS: Forty-four patients had a venous access port placed at the time of this study. Patients underwent red cell exchange (n = 33), therapeutic plasma exchange (n = 6) or extracorporeal photopheresis (n = 5). Forty (90%) patients had autoimmune diseases and four (10%) had neoplastic processes. Clinical success was achieved in 42 (95.5%) patients. Average venous access port dwell time was 632 days (range = 42-1191 days). All therapies through the venous access ports were well tolerated and no patients reported pain or discomfort. Major complications were seen in nine (20.5%) patients-the majority (n = 7) of which were due to venous access port malfunction-and resolved with catheter revision. One (2.27%) major complication involved an infected venous access port, and one involved a large hematoma at the venous access port site. Minor complications were seen in eight (18.2%) patients, where simple flushing of the catheter with saline or tissue plasminogen activator resolved the issue. CONCLUSION: The dual-chambered venous access port was successfully used for sustained blood flow in apheresis therapy with a moderate, yet correctable complication rate.

Optimizing Image Quality When Evaluating Blood Flow at Doppler US: A Tutorial.

Doppler US is an essential component of nearly all diagnostic US procedures. In this era of increased awareness of the effects of ionizing radiation and the side effects of iodine- and gadolinium-based contrast agents, Doppler US is poised to play an even bigger role in medical imaging. It is safe, cost-effective, portable, and highly accurate when performed by an experienced operator. The sensitivities and specificities of Doppler US for detecting blood flow and determining the direction and velocity of blood flow in various organs and vascular systems have increased dramatically in the past decade. With use of advanced flow techniques that are available for use with most modern equipment, US can provide vascular information that is comparable to or even more accurate than that obtained with other cross-sectional and interventional modalities. However, there remains concern that US (including newer more advanced flow-evaluating techniques) will not be used to its full potential owing to dependence on operator skill and expertise. Thorough understanding of image optimization techniques and expanded knowledge of the physical principles, instrumentation, application, advantages, and limitations of this modality are of utmost importance. The authors provide a simple practical guide for optimizing images for vascular flow detection by reviewing various cases and focusing on the parameters that should be optimized. Online supplemental material is available for this article. ©RSNA, 2019 See discussion on this article by Pellerito.

Predicting Treatment Response to Intra-arterial Therapies for Hepatocellular Carcinoma with the Use of Supervised Machine Learning-An Artificial Intelligence Concept.

PURPOSE: To use magnetic resonance (MR) imaging and clinical patient data to create an artificial intelligence (AI) framework for the prediction of therapeutic outcomes of transarterial chemoembolization by applying machine learning (ML) techniques. MATERIALS AND METHODS: This study included 36 patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization. The cohort (age 62 ± 8.9 years; 31 men; 13 white; 24 Eastern Cooperative Oncology Group performance status 0, 10 status 1, 2 status 2; 31 Child-Pugh stage A, 4 stage B, 1 stage C; 1 Barcelona Clinic Liver Cancer stage 0, 12 stage A, 10 stage B, 13 stage C; tumor size 5.2 ± 3.0 cm; number of tumors 2.6 ± 1.1; and 30 conventional transarterial chemoembolization, 6 with drug-eluting embolic agents). MR imaging was obtained before and 1 month after transarterial chemoembolization. Image-based tumor response to transarterial chemoembolization was assessed with the use of the 3D quantitative European Association for the Study of the Liver (qEASL) criterion. Clinical information, baseline imaging, and therapeutic features were used to train logistic regression (LR) and random forest (RF) models to predict patients as treatment responders or nonresponders under the qEASL response criterion. The performance of each model was validated using leave-one-out cross-validation. RESULTS: Both LR and RF models predicted transarterial chemoembolization treatment response with an overall accuracy of 78% (sensitivity 62.5%, specificity 82.1%, positive predictive value 50.0%, negative predictive value 88.5%). The strongest predictors of treatment response included a clinical variable (presence of cirrhosis) and an imaging variable (relative tumor signal intensity >27.0). CONCLUSIONS: Transarterial chemoembolization outcomes in patients with HCC may be predicted before procedures by combining clinical patient data and baseline MR imaging with the use of AI and ML techniques.

Effects of zinc supplementation on antioxidant status and lipid peroxidation in hemodialysis patients.

OBJECTIVES: This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level. DESIGN AND SETTING: Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital. SUBJECTS: Sixty-five HD patients were randomly enrolled into 2 groups. INTERVENTION: Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months. MAIN OUTCOME MEASURES: Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method. RESULTS: The levels of serum zinc, TAC, GSH (P < .001 for all), and SOD activity (P < .001 for group A and P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period (P = .003 for group A and P < .001 for group B). CONCLUSIONS: Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients.

Paraoxonase enzyme activity is enhanced by zinc supplementation in hemodialysis patients.

BACKGROUND AND AIMS: Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD. METHODS: This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits. RESULTS: In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased (p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased (p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group. CONCLUSIONS: Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients.

Protective effect of grape seed extract on gentamicin-induced acute kidney injury.

INTRODUCTION. This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHODS. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. RESULTS. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P < .001). CONCLUSIONS. This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury.

Supplemental food may not prevent iron-deficiency anemia in infants.

OBJECTIVE: The present study evaluates the role of supplementary food and medicinal iron intake in preventing iron deficiency anemia in children aged between 4 to 6 months. METHODS: During a case-control study in "Tabriz Children Hospital", nutritional and medicinal-iron intake of 60 consecutively selected patients with iron-deficiency anemia were compared with 60 non-anemic children of similar age and sex distributions. RESULTS: The mean hemoglobin concentration, corpuscular volume and serum iron were 9.11 g/dl, 65.41 fL and 19.33 microg/dl, in case group; and 12.6 g/dl, 75.18 fL and 78.28 microg/dl, in control group, respectively. There was no statistically significant difference between age of case and control groups when complementary-semisolid foods were started (P=0.058), but the mean of received medicinal iron in case group was significantly lower than control group (P<0.001). CONCLUSION: Supplementary food intake alone is not efficient to prevent iron deficiency anemia since the age of 4-6 months. So, regular administration of medicinal iron is crucial to prevent iron-deficiency anemia in children aged 4-6 months.