Physical Examination and Ultrasound Evaluation of Patients with Superficial Venous Disease.

Systematic and standardized evaluation of superficial venous disease, guided by knowledge of the various clinical presentations, venous anatomy, and pathophysiology of reflux, is essential for appropriate diagnosis and optimal treatment. Duplex ultrasonography is the standard for delineating venous anatomy, detecting anatomic variants, and identifying the origin of venous insufficiency. This article reviews tools and techniques essential for physical examination and ultrasound assessment of patients with superficial venous disease.

Assessing ablation margins of FDG-avid liver tumors during PET/CT-guided thermal ablation procedures: a retrospective study.

BACKGROUND: To retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes. METHODS: Fifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1-49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors. RESULTS: Minimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm. CONCLUSION: Breath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.

Genicular Artery Embolization for Osteoarthritis Related Knee Pain: A Systematic Review and Qualitative Analysis of Clinical Outcomes.

Objective To systematically review the published literature on genicular artery embolization (GAE) for osteoarthritis (OA) related knee pain. Materials and Methods Using three databases, a systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcome measures included the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results Three single-arm studies were included from an initial search yielding 305 results. One hundred and eighty-six knees in 133 patients with either mild-to-moderate (174/186, 94%) or severe (12/186, 6%) OA underwent embolization with either imipenem/cilastatin sodium (159/186, 85%) or embozene (27/186, 15%). Technical success was 100%. Average VAS improved from baseline at 1 day, 1 week, 1 month, 3 months, 4 months, 6 months, 1 year and 2 years (66.5 at baseline vs 33.5, 32.7, 33.8, 28.9, 29.0, 22.3, 14.8 and 14.0, respectively). Average WOMAC scores improved from baseline at 1, 3, 4, 6, 12 and 24 months (45.7 at baseline vs 24.0, 31.0, 14.8, 14.6, 8.2 and 6.2). Severe OA in 12 cases showed initially improved VAS, but was not sustained. Minor adverse events such as erythema in the region of embolization (21/186, 11%), puncture-site hematoma (18/186, 10%), paresthesia (2/186, 1%) and fever (1/186, 0.5%) were reported. Conclusion Limited single-arm studies report GAE is promising for treating OA-related pain. Most treatments performed for mild-to-moderate OA demonstrated durable clinical responses from 6 months to 4 years. Limited data for severe OA suggest a non-durable response. Future studies should be standardized to facilitate comparison and control for placebo effect.

Intraprocedural Ablation Margin Assessment by Using Ammonia Perfusion PET during FDG PET/CT-guided Liver Tumor Ablation: A Pilot Study.

Purpose To prospectively determine whether nitrogen 13 (13N) ammonia perfusion positron emission tomography (PET) during fluorine 18 fluorodeoxyglucose (FDG) PET/computed tomography (CT)-guided liver tumor ablation can be used to intraprocedurally assess ablation margins. Materials and Methods Eight patients (five women and three men; age range, 36-74 years; mean age, 57 years) were enrolled in this pilot study and underwent FDG PET/CT-guided microwave ablation of 11 FDG-avid liver metastases (mean diameter, 22 mm; range, 11-34 mm). All procedures were performed between March 2014 and December 2016. Complete ablation margin visibility and minimum ablation margin thickness were assessed by using intraprocedural 13N-ammonia perfusion PET compared with 24-hour postprocedural MR imaging by two independent blinded radiologists. Local tumor progression for each ablated tumor was assessed at follow-up imaging for 3-38 months (median, 17.6 months). Descriptive analysis was performed. Results Eleven of 11 (100%) ablation margins were fully assessable by using intraprocedural perfusion PET by both readers; six of eleven (55%) margins were fully assessable by both readers at postprocedural 24-hour MR imaging. By using perfusion PET, one tumor that had been judged by both readers to have a minimum margin of 0 mm progressed locally. No tumors judged to have a minimum margin greater than 0 mm at perfusion PET progressed locally. Conclusion 13N-ammonia perfusion PET during FDG PET/CT-guided liver tumor ablations can potentially be used to intraprocedurally assess the entire ablation margin, including the minimum margin. © RSNA, 2018.

Correlation of Doxorubicin Delivery and Tumor Necrosis after Drug-eluting Bead Transarterial Chemoembolization of Rabbit VX2 Liver Tumors.

Purpose To quantify the correlation between doxorubicin (DOX) delivery and tumor necrosis after drug-eluting bead (DEB) transarterial chemoembolization (TACE). Materials and Methods In this animal care committee-approved study, New Zealand white rabbit VX2 liver tumors were treated transarterially with DOX-loaded 70-150-µm DEBs in five treatment groups with varying drug doses: sham (saline), 0 mg, 12.5 mg, 25 mg, and 37.5 mg. DEB TACE was followed by 3- and 7-day sacrifice, tumor harvest, and sectioning. Drug delivery was assessed by using fluorescence imaging, and tumor necrosis was quantified by means of histologic analysis. Statistical correlation of DOX delivery and tumor necrosis was performed by using the Spearman rank correlation coefficient (ρ). Results Thirty-six VX2 tumors (median diameter, 1.3 cm) in 20 rabbits (median weight, 2.8 kg) underwent successful DEB TACE. Treatment groups included eight, seven, eight, five, and eight tumors of similar size (P > .05). Tumors showed progressively greater DOX extent (sham, 0%; 0 mg, 0%; 12.5 mg, 3%; 25 mg, 20%; and 37.5 mg, 27%) and intensity (sham, 0.4; 0 mg, 1.9; 12.5 mg, 8.5; 25 mg, 9.6; and 37.5 mg, 18.3) and higher median percentage necrosis (sham, 68%; 0 mg, 64%; 12.5 mg, 76%; 25 mg, 78%; and 37.5 mg, 83%) across DOX treatment groups. Correlation of DOX extent (ρ = 0.975, P = .005) and intensity (ρ = 0.900, P = .037) with percentage tumor necrosis was statistically significant. Conclusion Incremental increases in DOX correlate with greater necrosis in rabbit VX2 liver tumors after DEB TACE. This result indicates an essential role for chemotherapy-induced cytotoxicity in TACE effectiveness and supports the use of chemotherapeutic drugs in transarterial therapy. (©) RSNA, 2016 Online supplemental material is available for this article.

Conventional Ethiodized Oil Transarterial Chemoembolization for Treatment of Hepatocellular Carcinoma: Contemporary Single-Center Review of Clinical Outcomes.

OBJECTIVE: The purpose of this study is to investigate the outcomes of conventional transarterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) in contemporary clinical practice. MATERIALS AND METHODS: In this single-institution retrospective study, 188 patients underwent conventional TACE for HCC between 2007 and 2013. Medical record and imaging review was used to collect baseline demographic and disease data, tumor response, time to progression (TTP), and progression-free survival (PFS) outcomes, as well as transplant-free survival, calculated from the time of the first conventional TACE treatment. Data were censored in April 2014. RESULTS: The study cohort included 140 men and 48 women (mean age, 60 years; Barcelona Clinic Liver Cancer [BCLC] stage 0 = 5%, BCLC stage A = 41%, BCLC stage B = 28%, BCLC stage C = 15%, and BCLC stage D = 11%) with 207 index tumors (mean size, 4.0 cm; 11% with portal vein invasion) treated with a mean of 1.6 selective (79%) or lobar (21%) conventional TACE sessions. Concurrent thermal ablation was performed for 19% of patients. Objective response rates included size response in 29% (World Health Organization) and 28% (Response Evaluation Criteria for Solid Tumors [RECIST]) of patients, and necrosis response in 79% (European Association for the Study of the Liver) and 70% (modified RECIST) of patients. Median local TTP, distant site TTP, local PFS, and other site PFS were 51.7, 11.2, 10.8, and 10.5 months. Eighteen percent of patients underwent liver transplantation; 48% of United Network for Organ Sharing stage T3 tumors were downstaged to stage T2. Transplant-free survival for the entire cohort was 16.8 months (not reached, 33.9, 16.0, 4.4, and 6.9 months for BCLC stages 0, A, B, C, and D, respectively). Postembolization syndrome requiring extended hospital stay or readmission occurred in only 6% of patients. CONCLUSION: Conventional TACE is effective and safe for HCC therapy and may confer a survival benefit. The current data are in line with reported conventional TACE outcomes, and the minor postembolization syndrome incidence supports the low morbidity of this approach.

MELD score for prediction of survival after emergent TIPS for acute variceal hemorrhage: derivation and validation in a 101-patient cohort.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: The Model for End Stage Liver Disease (MELD) score has not been derived and validated for the emergent transjugular intrahepatic portosystemic shunt (TIPS) population. We sought to identify predictive factors for survival among emergent TIPS patients, and to substantiate MELD for outcomes prognostication in this population. RESULTS: 101 patients with acute life threatening variceal hemorrhage underwent emergent TIPS (defined by failed endoscopic therapy for active bleeding, acute hemoglobin drop, ≥ 2-unit transfusion requirement, and/or vasopressor need) at between 1998-2013. Demographic, clinical, laboratory, and procedure parameters were analyzed for correlation with mortality using Cox proportional hazards regression to derive the prognostic value of MELD constituents. Area under receiver operator characteristic (AUROC) curves was used to assess the capability of MELD prediction of mortality. TIPS were created 119 ± 167 h after initial bleeding events. Hemodynamic success was achieved in 90%. Median final portosystemic pressure gradient was 8 mmHg. Variceal rebleeding incidence was 21%. The four original MELD components showed significant correlation with mortality on multivariate Cox regression: baseline bilirubin (regression coefficient 0.366), creatinine (0.621), international normalized ratio (1.111), and liver disease etiology (0.808), validating the MELD system for emergent cases. No other significant predictive parameters were identified. MELD was an excellent predictor of 90-day mortality in the emergent TIPS population (AUROC = 0.842, 95% CI 0.755-0.928). CONCLUSIONS: Based on independent derivation of prognostic constituents and confirmation of predictive accuracy, MELD is a valid and reliable metric for risk stratification and survival projection after emergent TIPS.

Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

PURPOSE: Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. METHODS: A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. RESULTS: Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 µg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 µg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. CONCLUSION: While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

Gene expression in hepatocellular carcinoma: pilot study of potential transarterial chemoembolization response biomarkers.

PURPOSE: To perform a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy. MATERIALS AND METHODS: In this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease, and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR). RESULTS: The study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49-3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels. CONCLUSIONS: Genetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration of their respective predictive capacity thresholds is necessary.

Should transjugular intrahepatic portosystemic shunt stent grafts be underdilated?

Although underdilation of transjugular intrahepatic portosystemic shunt (TIPS) stent grafts is commonly performed to limit complications arising from excessive portosystemic shunting, it is uncertain whether underdilated stents retain their smaller diameter indefinitely or eventually expand to nominal caliber. In this investigation, postprocedure computed tomography (CT) was used to compare diameters of underdilated TIPSs and TIPSs expanded to a nominal diameter of 10 mm in 61 cases. The groups had comparable shunt diameters on post-TIPS imaging (9.8 mm vs 9.9 mm; P = .079), with similar incidences of hepatic encephalopathy (34% vs 20%; P = .372), indicating stent self-expansion over time, and bringing into question the advantages of underdilation for customization of shunt caliber.

Clearing the Confusion over Hepatic Encephalopathy After TIPS Creation: Incidence, Prognostic Factors, and Clinical Outcomes.

PURPOSE: To assess the incidence, prognostic factors, and clinical outcomes of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this single-institution retrospective study, 191 patients (m:f = 114:77, median age 54 years, median Model for End-Stage Liver Disease or MELD score 14) who underwent TIPS creation between 1999 and 2013 were studied. Medical record review was used to identify demographic characteristics, liver disease, procedure, and outcome data. Post-TIPS HE within 30 days was defined by new mental status changes and was graded according to the West Haven classification system. The influence of data parameters on HE occurrence and 90-day mortality was assessed using binary logistic regression. RESULTS: TIPS was successfully created with hemodynamic success in 99 % of cases. Median final PSG was 7 mmHg. HE incidence within 30 days was 42 % (81/191; 22 % de novo, 12 % stable, and 8 % worsening). Degrees of HE included grade 1 (46 %), grade 2 (29 %), grade 3 (18 %), and grade 4 (7 %). Medical therapy typically addressed HE, and shunt reduction was necessary in only three cases. MELD score (P = 0.020) and age (P = 0.009) were significantly associated with HE development on multivariate analysis. Occurrence of de novo HE post-TIPS did not associate with 90-day mortality (P = 0.400), in contrast to worsening HE (P < 0.001). CONCLUSIONS: The incidence of post-TIPS HE is non-trivial, but symptoms are typically mild and medically managed. HE rates are higher in older patients and those with worse liver function and should be contemplated when counseling on expected TIPS outcomes and post-procedure course.

Characterization of liver function parameter alterations after transjugular intrahepatic portosystemic shunt creation and association with early mortality.

OBJECTIVE: The purpose of this article is to characterize the temporal evolution and clinical impact of laboratory liver function parameters after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this single-institution retrospective study, 157 patients (98 men and 59 women; median age, 55 years) underwent TIPS between 2000 and 2012 and had 1-month hepatobiliary laboratory follow-up. Medical record review was used to compare baseline, peak, and low bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and international normalized ratio (INR) levels within 30 days after TIPS in surviving and dying patients to assess laboratory responses to shunt creation. RESULTS: TIPSs were created with a hemodynamic success rate of 98%, with median pressure gradient reduction of 13 mm Hg. Ninety-day mortality was 21%. Hepatobiliary laboratory values showed significant increases in the days after TIPS compared with baseline levels (bilirubin, 1.6 vs 3.5 mg/dL; AST, 49 vs 149 U/L; ALT, 26 vs 90 U/L; alkaline phosphatase, 97 vs 177 U/L; and INR, 1.5 vs 2.0; p<0.05 in all cases). Patients surviving to 90 days experienced statistically significant but transient laboratory value elevations-up to twofold over baseline-within days of TIPS, whereas patients dying within 90 days experienced three-to fourfold increases over a longer period that did not return to baseline. Differences in laboratory evolution were statistically significant in surviving versus dying patients. CONCLUSION: TIPS results in acute transient elevation of hepatobiliary enzymes, which may be more pronounced in patients with early mortality. An exaggerated laboratory elevation in excess of threefold greater than baseline or a prolonged increase exceeding 1 week may herald poorer clinical outcome.

Percutaneous Portosystemic Shunts: TIPS and Beyond.

Percutaneous interventions for portal hypertension have been available since the 1990s. Over time, improved technology-including covered stent grafts-and clinical understanding has expanded the available procedures for percutaneous portal decompression. While transjugular intrahepatic portosystemic shunt creation is the most commonly cited percutaneous intervention, direct intrahepatic portocaval shunt and percutaneous mesocaval shunt creation are important alternatives with specific advantages and applications. This article reviews contemporary, minimally invasive interventional approaches to percutaneous portosystemic shunt creation in terms of procedure rationale, patient selection, interventional technique, and technical outcomes.

Development, growth, propagation, and angiographic utilization of the rabbit VX2 model of liver cancer: a pictorial primer and "how to" guide.

The VX2 tumor is a leporine anaplastic squamous cell carcinoma characterized by rapid growth, hypervascularity, and facile propagation in the skeletal muscle. Since its introduction over 70 years ago, it has been used to model a variety of malignancies, and is commonly employed by interventional radiologists in preclinical investigations of hepatocellular carcinoma. However, despite the widespread and lasting popularity of the model, there are few technical resources detailing its use. Herein, we present a comprehensive pictorial outline of the technical methodology for development, growth, propagation, and angiographic utilization of the rabbit VX2 liver tumor model.

Characteristics of primary and secondary hepatic malignancies associated with hepatopulmonary shunting.

PURPOSE: To identify liver tumor characteristics associated with low (<10%), intermediate (10%-20%), and high (>20%) lung shunt fraction (LSF) at technetium 99m ((99m)Tc) macroaggregated albumin (MAA) imaging performed before yttrium 90 ((90)Y) radioembolization (RE). MATERIALS AND METHODS: In this single-center retrospective study, 141 patients (70 with hepatocellular carcinoma [HCC], 71 with other tumors; 95 men, 45 women; median age, 61 years) underwent mapping arteriography with (99m)Tc-MAA LSF calculation before (90)Y RE from 2006 to 2012. Tumor characteristics, including tumor type, index lesion size and morphologic structure (circumscribed, infiltrative), focality (solitary oligonodular, multinodular), disease distribution (unilobar, bilobar), tumor burden (≤50%, 50%), portal vein invasion (present, absent), and arterioportal shunting (present, absent) were correlated with (99m)Tc-MAA imaging-calculated LSFs at univariate and multivariate analysis. RESULTS: Median LSF was 8.4% (HCC, 9.0%; other tumors, 8.3%). LSF greater than 20% occurred in 14% of HCCs, but only in 3% of other tumors (P = .004). For HCC, tumor morphologic structure (P = .022), tumor burden (P < .001), main portal vein invasion (P = .033), and arterioportal shunting (P < .001) were significantly associated with different LSF categories at univariate analysis; infiltrative morphologic structure, tumor burden greater than 50%, portal vein invasion, and shunting had confirmed association with high LSF at multivariate analysis. For other liver tumors, tumor size (P = .001) and tumor burden (P = .003) were significantly associated with different LSF categories at univariate analysis. Multivariate confirmation was precluded by small sample size. Patients underwent a median of one (90)Y RE session (range, one to six), with median per-treatment and cumulative lung doses of 6.0 Gy and 8.5 Gy, respectively. CONCLUSION: LSF greater than 20% periodically occurs in HCC but is uncommon in other liver tumors. Specific tumor characteristics are associated with LSF greater than 20% and may indicate need for interventions to reduce LSF.